Molecules

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Open AccessArticle

A Sub-Pathway Based Method to Identify Candidate Agents for Ankylosing Spondylitis

by Kai Chen, Yingchuan Zhao, Yu Chen, Chuanfeng Wang, Ziqiang Chen, Yushu Bai, Xiaodong Zhu and Ming Li

Molecules 2012, 17(10), 12460-12468; https://doi.org/10.3390/molecules171012460 - 22 Oct 2012

Cited by 3 | Viewed by 6306

Abstract

The need for new therapeutics for Ankylosing Spondylitis (AS) is highlighted by the general lack of efficacy for most agents currently available for this disease. Many recent studies have detailed molecular pathways in AS, and several molecule-targeting agents are undergoing evaluation. We aimed [...] Read more.

The need for new therapeutics for Ankylosing Spondylitis (AS) is highlighted by the general lack of efficacy for most agents currently available for this disease. Many recent studies have detailed molecular pathways in AS, and several molecule-targeting agents are undergoing evaluation. We aimed to explore the mechanism of AS and identify biologically active small molecules capable of targeting the sub-pathways which were disregulated in the development of AS. By using the GSE25101 microarray data accessible from the Gene Expression Omnibus database, we first identified the differentially expressed genes (DEGs) between AS samples and healthy controls, followed by the sub-pathway enrichment analysis of the DEGs. In addition, we propose the use of an approach based on targeting sub-pathways to identify potential agents for AS. A total of 3,280 genes were identified as being significantly different between patients and controls with p-values < 0.1. Our study showed that neurotrophic signaling pathway and some immune-associated pathways may be involved in the development of AS. Besides, our bioinformatics analysis revealed a total of 15 small molecules which may play a role in perturbing the development of AS. Our study proposes the use of an approach based on targeting sub-pathways to identify potential agents for AS. Candidate agents identified by our approach may provide the groundwork for a combination therapy approach for AS. Full article

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Open AccessArticle

Acute Toxicity and Gastroprotective Effect of the Schiff Base Ligand 1H-Indole-3-ethylene-5-nitrosalicylaldimine and Its Nickel (II) Complex on Ethanol Induced Gastric Lesions in Rats

by Mohamed Mustafa Ibrahim, Hapipah Mohd Ali, Mahmood Ameen Abdullah and Pouya Hassandarvish

Molecules 2012, 17(10), 12449-12459; https://doi.org/10.3390/molecules171012449 - 22 Oct 2012

Cited by 25 | Viewed by 7671

Abstract

The present study was performed to evaluate the gastroprotective activity of Schiff base ligand derived from the condensation reaction of tryptamine (an indole derivative) and 5-nitrosalicylaldehyde (TNS) and its nickel (II) complex against ethanol-induced gastric ulcer in rats. The compounds were orally administered [...] Read more.

The present study was performed to evaluate the gastroprotective activity of Schiff base ligand derived from the condensation reaction of tryptamine (an indole derivative) and 5-nitrosalicylaldehyde (TNS) and its nickel (II) complex against ethanol-induced gastric ulcer in rats. The compounds were orally administered with low (30 mg/kg) and high (60 mg/kg) doses to ulcer-induced Sprague-Dawley rats. Macroscopically, the ulcer control group exhibited severe mucosal injury, whereas pre-treatment with either cimetidine or TNS and its nickel (II) complex each resulted in significant protection against gastric mucosal injury. Flattening of gastric mucosal folds was also observed in rats pretreated with TNS and its nickel complex. Histological studies of the gastric wall of ulcer control group revealed severe damage of gastric mucosa, along with edema and leucocytes infiltration of the submucosal layer compared to rats pre-treated with either cimetidine or TNS and its nickel (II) compound, where there was marked gastric protection along with reduction of edema and leucocytes infiltration of the submucosal layer. Acute toxicity study done on mice with a higher dose of 5 g/kg of TNS and its nickel (II) complex did not manifest any toxicological signs. Research finding suggest that TNS and its nickel (II) complex could be considered as effective gastroprotective compounds. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessArticle

Synthesis, FTIR, ¹³C-NMR and Temperature-Dependent ¹H‑NMR Characteristics of Bis-naphthalimide Derivatives

by Waldemar Grzesiak and Bogumił Brycki

Molecules 2012, 17(10), 12427-12448; https://doi.org/10.3390/molecules171012427 - 22 Oct 2012

Cited by 6 | Viewed by 11556

Abstract

Chemotherapy is still the most important method of cancer treatment. To make this method more effective and safe, new drugs to destroy cancer cells are needed. Some bis-naphthalimide derivatives show potential anticancer activity via an intercalation mechanism. A higher degree of DNA intercalation [...] Read more.

Chemotherapy is still the most important method of cancer treatment. To make this method more effective and safe, new drugs to destroy cancer cells are needed. Some bis-naphthalimide derivatives show potential anticancer activity via an intercalation mechanism. A higher degree of DNA intercalation corresponds to better therapeutic effects. The degree of intercalation of naphthalimides depends on their structure, molecular dynamics and intermolecular interactions with DNA. In order to apply any active substance as a drug, its molecular dynamics as well as possible interactions with target molecules have to be examined in exhaustive details. This paper describes a practical preparation of some novel bis-naphthalimide derivatives with different functional groups and their FTIR and ¹H- and ¹³C-NMR spectral characteristics. To determine the molecular dynamics of the obtained compounds the temperature, their ¹H-NMR spectra were measured. It has been clearly proven in this paper that the unusual temperature-dependent ¹H-NMR behaviorof the aromatic protons of phthalimide derivatives, previously described in the literature as “hypersensitivity” and explained by n-π interactions and molecular motions of aromatic amide rings, is a result of temperature driven changes of the geometry of carbonyl groups. Full article

(This article belongs to the Section Organic Chemistry)

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2059 KiB

Open AccessArticle

The Effect of Curcumin on Human Bronchial Epithelial Cells Exposed to Fine Particulate Matter: A Predictive Analysis

by Zhiguo Zhang, Xuyan Niu, Cheng Lu, Miao Jiang, Gary G. Xiao and Aiping Lu

Molecules 2012, 17(10), 12406-12426; https://doi.org/10.3390/molecules171012406 - 22 Oct 2012

Cited by 11 | Viewed by 8267

Abstract

Fine particulate matter (PM_2.5) has been associated in humans with inflammation, oxidative stress and cancer. Studies had shown that curcumin could potentially inhibit these effects; however, there had been no in vivo or in vitro reports about the effects of curcumin [...] Read more.

Fine particulate matter (PM_2.5) has been associated in humans with inflammation, oxidative stress and cancer. Studies had shown that curcumin could potentially inhibit these effects; however, there had been no in vivo or in vitro reports about the effects of curcumin on organisms exposed to PM_2.5. This predictive study explored the possible biological functions and pathways involved in the mechanism of curcumin inhibition of the hazardous effects of PM_2.5. For predictive analysis, microarray data were used to investigate the effect of PM_2.5 on human bronchial epithelial cells (HBEC), and human target proteins of curcumin were retrieved from PubChem. Two protein-protein interaction (PPI) networks were established based upon differential genes and target proteins, respectively, and the common network of these two networks was found. Functional and pathway analysis of the common network was performed using the Ingenuity Pathways Analysis (IPA) software. The results suggested that the predictive effects of curcumin on HBEC exposed to PM_2.5 were involved in bio-functions, including inflammatory response of airway, cancerogenesis, and apoptosis, and in pathways such as cancer, glucocorticoid receptor signaling, and NF-kappaB signaling. This study predicted for the first time that curcumin could be a potential therapeutic agent for protecting the human airway from the hazardous effects of PM_2.5. Full article

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Open AccessArticle

trans-Resveratrol in Nutraceuticals: Issues in Retail Quality and Effectiveness

by Damiano Rossi, Alessandra Guerrini, Renato Bruni, Eleonora Brognara, Monica Borgatti, Roberto Gambari, Silvia Maietti and Gianni Sacchetti

Molecules 2012, 17(10), 12393-12405; https://doi.org/10.3390/molecules171012393 - 22 Oct 2012

Cited by 52 | Viewed by 16153

Abstract

Fourteen brands of resveratrol-containing nutraceuticals were evaluated in order to verify their actual resveratrol content and to control if their health-promoting properties are related to manufacturing quality. Products included pure resveratrol capsules or multi-ingredient formulations with standardized amounts of resveratrol and other phytochemicals. [...] Read more.

Fourteen brands of resveratrol-containing nutraceuticals were evaluated in order to verify their actual resveratrol content and to control if their health-promoting properties are related to manufacturing quality. Products included pure resveratrol capsules or multi-ingredient formulations with standardized amounts of resveratrol and other phytochemicals. Samples were analyzed for total trans-resveratrol, flavonoids, procyanidin, polyphenol content and the results were compared with the content declared on-label. Only five out of 14 brands had near label values, compliant with Good Manufacturing Practices (GMP) requirements (95–105% content of active constituent), four products were slightly out of this range (83–111%) and three were in the 8–64% range. Two samples were below the limit of detection. The greater the difference between actual and labeled resveratrol content, the lower was the antioxidant and antiproliferative activity strength. Dietary supplements containing pure trans-resveratrol exhibited a greater induction of differentiation towards human leukemic K562 cells when compared to multicomponent products. Great differences currently exist among resveratrol food supplements commercially available and GMP-grade quality should not be taken for granted. On the other side, dosages suggested by most “pure”, “high-dosage” supplements may allow a supplementation level adequate to obtain some of the purported health benefits. Full article

(This article belongs to the Special Issue Methods in Polyphenol Analysis)

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Open AccessArticle

Synthesis of a Cholesteryl-HEG Phosphoramidite Derivative and Its Application to Lipid-conjugates of the Anti-HIV ^5'TGGGAG^3' Hotoda’s Sequence

by Domenica Musumeci and Daniela Montesarchio

Molecules 2012, 17(10), 12378-12392; https://doi.org/10.3390/molecules171012378 - 22 Oct 2012

Cited by 12 | Viewed by 9244

Abstract

A novel phosphoramidite derivative of cholesterol, with an ether-linked hexaethylene glycol (HEG) spacer arm, has been obtained through simple and reproducible solid phase modified oligonucleotide synthesis manipulations. This building block and the known phosphoramidite derivative of 3b-(2-hydroxyethoxy)cholesterol have been exploited in standard oligonucleotide [...] Read more.

A novel phosphoramidite derivative of cholesterol, with an ether-linked hexaethylene glycol (HEG) spacer arm, has been obtained through simple and reproducible solid phase modified oligonucleotide synthesis manipulations. This building block and the known phosphoramidite derivative of 3b-(2-hydroxyethoxy)cholesterol have been exploited in standard oligonucleotide synthesis protocols for the preparation of 5'- conjugates of the G-quadruplex-forming ^5'TGGGAG³^' oligomer, known as the Hotoda’s sequence, to produce new potential anti-HIV agents. Full article

(This article belongs to the Special Issue Nucleic Acid Analogs)

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Open AccessArticle

Phenylmethimazole Blocks dsRNA-Induced IRF3 Nuclear Translocation and Homodimerization

by Maria C. Courreges, Noriko Kantake, Douglas J. Goetz, Frank L. Schwartz and Kelly D. McCall

Molecules 2012, 17(10), 12365-12377; https://doi.org/10.3390/molecules171012365 - 22 Oct 2012

Cited by 14 | Viewed by 8319

Abstract

Previous studies revealed that phenylmethimazole (C10) inhibits IRF3 signaling, preventing dsRNA-induction of type 1 interferon gene expression, production, and downstream signaling. In the present study, we investigated the molecular basis for C10 inhibition of dsRNA-stimulated IRF3 signaling. IRF-3 Trans-AM assays were used to [...] Read more.

Previous studies revealed that phenylmethimazole (C10) inhibits IRF3 signaling, preventing dsRNA-induction of type 1 interferon gene expression, production, and downstream signaling. In the present study, we investigated the molecular basis for C10 inhibition of dsRNA-stimulated IRF3 signaling. IRF-3 Trans-AM assays were used to measure C10 effects on dsRNA induction of IRF3 DNA binding. Green fluorescent protein-labeled IRF3 was used to measure C10 effects on dsRNA-induced IRF3 nuclear translocation. Native PAGE, SDS PAGE, and western blotting were used to identify effects of C10 on IRF3 homodimer formation and phosphorylation, respectively. There was a significant impairment of dsRNA-induced IRF3 DNA binding activity in human embryonic kidney and pancreatic cancer cells with C10 treatment. C10 also blocked dsRNA-induced IRF3 nuclear translocation and homodimer formation without blocking serine 396 phosphorylation of IRF3. Together, these results indicate that C10 interferes with IRF3 signaling by blocking dsRNA-induced IRF3 homodimer formation, a prerequisite for nuclear translocation and DNA binding activities. Full article

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Open AccessArticle

Two New Cholic Acid Derivatives from the Marine Ascidian-Associated Bacterium Hasllibacter halocynthiae

by Sung Hun Kim, Yun Kyung Shin, Young Chang Sohn and Hak Cheol Kwon

Molecules 2012, 17(10), 12357-12364; https://doi.org/10.3390/molecules171012357 - 22 Oct 2012

Cited by 8 | Viewed by 6600

Abstract

The investigation of secondary metabolites in liquid cultures of a recently discovered marine bacterium, Hasllibacter halocynthiae strain KME 002^T, led to the isolation of two new cholic acid derivatives. The structures of these compounds were determined to be 3,3,12-trihydroxy-7-ketocholanic acid ( [...] Read more.

The investigation of secondary metabolites in liquid cultures of a recently discovered marine bacterium, Hasllibacter halocynthiae strain KME 002^T, led to the isolation of two new cholic acid derivatives. The structures of these compounds were determined to be 3,3,12-trihydroxy-7-ketocholanic acid (1) and 3,3,12-trihydroxy-7-deoxycholanic acid (2) through HRFABMS and NMR data analyses. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Comparison of the Phenolic Compounds, Carotenoids and Tocochromanols Content in Wheat Grain under Organic and Mineral Fertilization Regimes

by Iwona Konopka, Małgorzata Tańska, Alicja Faron, Arkadiusz Stępień and Katarzyna Wojtkowiak

Molecules 2012, 17(10), 12341-12356; https://doi.org/10.3390/molecules171012341 - 19 Oct 2012

Cited by 39 | Viewed by 9035

Abstract

A field study was performed to evaluate the effect of mineral (NPK) and organic-based fertilizers such as compost (C), manure (FYM) and meat and bone meal (MBM) on the appearance (dimensions and color) of spring wheat kernels and on the total content in [...] Read more.

A field study was performed to evaluate the effect of mineral (NPK) and organic-based fertilizers such as compost (C), manure (FYM) and meat and bone meal (MBM) on the appearance (dimensions and color) of spring wheat kernels and on the total content in grain of main its phytochemicals (polyphenols, carotenoids and tocochromanols) and phenolic acids composition. Total phenolic compounds were determined using the Folin-Ciocalteu assay after alkaline hydrolysis of grain and carotenoids were analyzed spectrophotometrically. Composition of tocochromanols and phenolic acids was determined using RP-HPLC techniques. Only insignificant differences in the appearance of kernels and small changes in the content and composition of grain phytochemicals were noted between the studied fertilization systems. Among the analyzed phytochemicals the greatest variation was observed in the group of polyphenol compounds, with a stated increase of their total content of 6.7 and 11.2% in grain fertilized with MBM and compost, respectively. Simultaneously the grain from organic fertilization contained significantly less phenolic acids, and the decrease in their content ranged from 10.0% for FYM to 24.8% for MBM+EM-1. Organically and conventionally fertilized grain had similar amounts of tocochromanols and carotenoids. Comparison of MBM and MBM+EM-1 variants showed that application of effective microorganisms decreased carotenoids and tocochromanols content by 8.5 and 9.7%, respectively. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Phenolic and Lignan Glycosides from the Butanol Extract of Averrhoa carambola L. Root

by Qingwei Wen, Xing Lin, Yeqi Liu, Xiaohui Xu, Tao Liang, Ni Zheng, Kintoko and Renbin Huang

Molecules 2012, 17(10), 12330-12340; https://doi.org/10.3390/molecules171012330 - 19 Oct 2012

Cited by 59 | Viewed by 6752

Abstract

Fifteen compounds, which included six chiral lignans and nine phenolic glycosides, were separated from the butanol fraction of Averrhoa carambola L. root and identified. All of the compounds, namely 3,4,5-trimethoxyphenol-1-O-β-D-glucopyranoside (1), benzyl-1-O-β- [...] Read more.

Fifteen compounds, which included six chiral lignans and nine phenolic glycosides, were separated from the butanol fraction of Averrhoa carambola L. root and identified. All of the compounds, namely 3,4,5-trimethoxyphenol-1-O-β-D-glucopyranoside (1), benzyl-1-O-β-D-glucopyranoside (2), (+)-5'-methoxyisolariciresinol 3α-O-β-D-gluco-pyranoside (3), (+)-isolariciresinol 3α-O-β-D-glucopyranoside (4), koaburaside (5), (+)-lyoniresinol 3α-O-β-D-glucopyranoside (6), (−)-lyoniresinol 3α-O-β-D-glucopyranoside (7), (−)-5'-methoxyisolariciresinol 3α-O-β-D-glucopyranoside (8), (−)-isolariciresinol 3α-O-β-D-glucopyranoside (9), 3,5-dimethoxy-4-hydroxyphenyl 1-O-β-apiofuranosyl (1''→6')-O-β-D-glucopyranoside (10), 3,4,5-trimethoxyphenyl 1-O-β-apiofuranosyl (1''→6')-β-gluco-pyranoside (11), methoxyhydroquinone-4-β-D-glucopyranoside (12), (2S)-2-O-β-D-gluco-pyranosyl-2-hydroxyphenylacetic acid (13), 3-hydroxy-4-methoxyphenol 1-O-β-D-apio-furanosyl-(1''→6')-O-β-D-glucopyranoside (14) and 4-hydroxy-3-methoxyphenol 1-O-β-D-apiofuranosyl-(1''→6')-O-β-D-glucopyranoside (15) were isolated from this plant for the first time. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

Bioassays Against Pinewood Nematode: Assessment of a Suitable Dilution Agent and Screening for Bioactive Essential Oils

by Pedro Barbosa, Jorge M. S. Faria, Marta D. Mendes, Luís Silva Dias, Maria Teresa Tinoco, José G. Barroso, Luis G. Pedro, Ana Cristina Figueiredo and Manuel Mota

Molecules 2012, 17(10), 12312-12329; https://doi.org/10.3390/molecules171012312 - 19 Oct 2012

Cited by 33 | Viewed by 7590

Abstract

Acetone was investigated and found to be an appropriate alternative to Triton X-100 as a solvent of essential oils in bioassays aimed to investigate their effects on pinewood nematode (Bursaphelenchus xylophilus) mortality. Therefore it was used as dilution agent to screen [...] Read more.

Acetone was investigated and found to be an appropriate alternative to Triton X-100 as a solvent of essential oils in bioassays aimed to investigate their effects on pinewood nematode (Bursaphelenchus xylophilus) mortality. Therefore it was used as dilution agent to screen the effectiveness of fifty two essential oils against this pest. Thirteen essential oils were highly effective, resulting in more than 90% pinewood nematode mortality at 2 mg/mL, with six of them resulting in 100% mortality. LC₁₀₀ values ranged between 0.50 mg/mL and 0.83 mg/mL for the essential oils of Origanum vulgare and Satureja montana, respectively. Essential oils were submitted to gas chromatography and gas chromatography-mass spectrometry analysis and their chemical composition established. Data from essential oils with 100% mortality at 2 mg/mL and other essential oils previously found to have LC₁₀₀ ≤ 2 mg/mL was combined, their chemical profiles investigated by correspondences analysis plus automatic classification. Full article

(This article belongs to the Section Natural Products Chemistry)

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Open AccessArticle

TLC Screening for Antioxidant Activity of Extracts from Fifteen Bamboo Species and Identification of Antioxidant Flavone Glycosides from Leaves of Bambusa. textilis McClure

by Jin Wang, Yong-De Yue, Feng Tang and Jia Sun

Molecules 2012, 17(10), 12297-12311; https://doi.org/10.3390/molecules171012297 - 19 Oct 2012

Cited by 70 | Viewed by 12705

Abstract

Interest in the antioxidant activity of bamboo leaves is growing. To discover new sources of natural antioxidants, a TLC bioautography method combined with a new image processing method was developed to evaluate the antioxidant activity of leaf extracts from 15 different species of [...] Read more.

Interest in the antioxidant activity of bamboo leaves is growing. To discover new sources of natural antioxidants, a TLC bioautography method combined with a new image processing method was developed to evaluate the antioxidant activity of leaf extracts from 15 different species of bamboo. The results showed that the methanolic extract of Bambusa. textilis McClure possessed the highest antioxidant activity among the selected bamboo species. To rapidly identify the antioxidant compounds, the crude extract of B. textilis McClure was analysed by HPLC-UV, and HPLC-micro-fractionation of the extract was carried out. Based on TLC bioautography-guided fractionation, three antioxidant fractions were isolated from B. textilis McClure by preparative chromatography. These three antioxidant compounds were identified as isoorientin 4''-O β-D-xylopyranoside (1), isoorientin 2''-O-α-L-rhamnoside (2) and isoorientin (3) according to their UV, MS, and NMR data. The proposed TLC screening method could therefore be an easy way to evaluate the antioxidant activity of bamboo leaves, and the results achieved should prove very helpful for promoting their utilization, as B. textilis McClure can be considered a promising plant source of natural antioxidants. Full article

(This article belongs to the Special Issue Antioxidants 2012)

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Open AccessArticle

Interaction Profile of Diphenyl Diselenide with Pharmacologically Significant Thiols

by Waseem Hassan and Joao Batista Teixeira Rocha

Molecules 2012, 17(10), 12287-12296; https://doi.org/10.3390/molecules171012287 - 19 Oct 2012

Cited by 20 | Viewed by 7378

Abstract

Diphenyl diselenide has shown interesting biological activities in various free-radical-induced damage models and can be considered as a potential candidate drug against oxidative stress. Apart from its anti-oxidant activity, this compound can oxidize various thiols. However there are no detailed studies in the [...] Read more.

Diphenyl diselenide has shown interesting biological activities in various free-radical-induced damage models and can be considered as a potential candidate drug against oxidative stress. Apart from its anti-oxidant activity, this compound can oxidize various thiols. However there are no detailed studies in the literature about the thiol oxidase-like activity of this compound against biologically significant mono and di-thiols with respect to various pH conditions. Keeping in mind the scarcity of data in this area of organochalcogen chemistry, we report for the first time the kinetics of thiol oxidation by diphenyl diselenide, which was carried out in a commonly used phosphate buffer, not only at physiological pH, but also at a number of acidic values. The relative reactivities of the different thiols with diphenyl diselenide were independent of the pKa of the thiol group, such that at pH 7.4, cysteine and dithiothreitol were the most reactive, while 2,3-dimercapto-1-propanesulfonic acid and glutathione were weakly reactive and extremely low reactivity was observed with dimercaptosuccinic acid. Rate of oxidation was dependent on the pH of the incubation medium. The results obtained will help us in the design of rational strategies for the safe pharmacological use of diphenyl diselenide. Full article

(This article belongs to the Section Molecular Diversity)

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Open AccessReview

Antimicrobial Peptides for Therapeutic Applications: A Review

by Min-Duk Seo, Hyung-Sik Won, Ji-Hun Kim, Tsogbadrakh Mishig-Ochir and Bong-Jin Lee

Molecules 2012, 17(10), 12276-12286; https://doi.org/10.3390/molecules171012276 - 18 Oct 2012

Cited by 413 | Viewed by 22893

Abstract

Antimicrobial peptides (AMPs) have been considered as potential therapeutic sources of future antibiotics because of their broad-spectrum activities and different mechanisms of action compared to conventional antibiotics. Although AMPs possess considerable benefits as new generation antibiotics, their clinical and commercial development still have [...] Read more.

Antimicrobial peptides (AMPs) have been considered as potential therapeutic sources of future antibiotics because of their broad-spectrum activities and different mechanisms of action compared to conventional antibiotics. Although AMPs possess considerable benefits as new generation antibiotics, their clinical and commercial development still have some limitations, such as potential toxicity, susceptibility to proteases, and high cost of peptide production. In order to overcome those obstacles, extensive efforts have been carried out. For instance, unusual amino acids or peptido-mimetics are introduced to avoid the proteolytic degradation and the design of short peptides retaining antimicrobial activities is proposed as a solution for the cost issue. In this review, we focus on small peptides, especially those with less than twelve amino acids, and provide an overview of the relationships between their three-dimensional structures and antimicrobial activities. The efforts to develop highly active AMPs with shorter sequences are also described. Full article

(This article belongs to the Special Issue Advances in Medicinal Chemistry of Antibiotics)

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Open AccessArticle

Design, Synthesis and in Vivo Anti-inflammatory Activities of 2,4-Diaryl-5-4H-imidazolone Derivatives

by Moustafa El-Araby, Abdelsattar Omar, Hassanein H. Hassanein, Abdel-Ghany H. El-Helby and Asharf A. Abdel-Rahman

Molecules 2012, 17(10), 12262-12275; https://doi.org/10.3390/molecules171012262 - 18 Oct 2012

Cited by 46 | Viewed by 8700

Abstract

A series of 2,4-diaryl-5(4H)-imidazolones were prepared and evaluated for their anti-inflammatory activities. Some selected 2,4-diaryl-5(4H)-imidazolones exhibited excellent anti-inflammatory activity in the carrageenan-induced rat paw edema model. Structure Activity Relationships within the series were studied. The substitution at the N [...] Read more.

A series of 2,4-diaryl-5(4H)-imidazolones were prepared and evaluated for their anti-inflammatory activities. Some selected 2,4-diaryl-5(4H)-imidazolones exhibited excellent anti-inflammatory activity in the carrageenan-induced rat paw edema model. Structure Activity Relationships within the series were studied. The substitution at the N-sulfonamide moiety by a small hydrophilic acetyl group resulted in compounds with superior in vivo anti-inflammatory properties. As expected from their COX-2 selectivity, most of the active compounds lacked gastrointestinal toxicity in vivo in rats after a 3-day treatment of 25 mg/kg/day. Full article

(This article belongs to the Section Medicinal Chemistry)

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Open AccessCommunication

First Example of a Lipophilic Porphyrin-Cardanol Hybrid Embedded in a Cardanol-Based Micellar Nanodispersion

by Ermelinda Bloise, Luigi Carbone, Giuseppe Colafemmina, Lucia D’Accolti, Selma Elaine Mazzetto, Giuseppe Vasapollo and Giuseppe Mele

Molecules 2012, 17(10), 12252-12261; https://doi.org/10.3390/molecules171012252 - 18 Oct 2012

Cited by 30 | Viewed by 8979

Abstract

Cardanol is a natural and renewable organic raw material obtained as the major chemical component by vacuum distillation of cashew nut shell liquid. In this work a new sustainable procedure for producing cardanol-based micellar nanodispersions having an embedded lipophilic porphyrin itself peripherally functionalized [...] Read more.

Cardanol is a natural and renewable organic raw material obtained as the major chemical component by vacuum distillation of cashew nut shell liquid. In this work a new sustainable procedure for producing cardanol-based micellar nanodispersions having an embedded lipophilic porphyrin itself peripherally functionalized with cardanol substituents (porphyrin-cardanol hybrid) has been described for the first time. In particular, cardanol acts as the solvent of the cardanol hybrid porphyrin and cholesterol as well as being the main component of the nanodispersions. In this way a “green” micellar nanodispersion, in which a high percentage of the micellar system is derived from renewable “functional” molecules, has been produced. Full article

(This article belongs to the Special Issue Tetrapyrroles, Porphyrins and Phthalocyanines)

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Open AccessArticle

Identification of Fungicidal 2,6-Disubstituted Quinolines with Activity against Candida Biofilms

by Nicolas Delattin, Dorothée Bardiot, Arnaud Marchand, Patrick Chaltin, Katrijn De Brucker, Bruno P. A. Cammue and Karin Thevissen

Molecules 2012, 17(10), 12243-12251; https://doi.org/10.3390/molecules171012243 - 18 Oct 2012

Cited by 10 | Viewed by 6729

Abstract

We have identified two subseries of 2,6-disubstituted quinolines, consisting of 6-amide and 6-urea derivatives, which are characterized by fungicidal activity against Candida albicans with minimal fungicidal concentration (MFC) values C. albicans, in particular compounds 1, 5 and 6 characterized by MFC values [...] Read more.

We have identified two subseries of 2,6-disubstituted quinolines, consisting of 6-amide and 6-urea derivatives, which are characterized by fungicidal activity against Candida albicans with minimal fungicidal concentration (MFC) values < 15 µM. The 6-amide derivatives displayed the highest fungicidal activity against C. albicans, in particular compounds 1, 5 and 6 characterized by MFC values of 6.25–12.5 µM. Compounds 1 and 5 of this series displayed fungicidal activity against the emerging pathogen Candida glabrata (MFC < 50 µM). The 6-amide derivatives 1, 2, 5, and 6 and the 6-urea derivatives 10, 12, 13 and 15 could also eradicate C. albicans biofilms. We found that the 6-urea derivatives 10, 13, and 15 induced accumulation of endogenous reactive oxygen species in Candida albicans biofilms. Full article

(This article belongs to the Special Issue Advances in Medicinal Chemistry of Antibiotics)

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Open AccessCommunication

Solvent-Free Synthesis of Modified Pectin Compounds Promoted by Microwave Irradiation

by Enrica Calce, Valeria Bugatti, Vittoria Vittoria and Stefania De Luca

Molecules 2012, 17(10), 12234-12242; https://doi.org/10.3390/molecules171012234 - 18 Oct 2012

Cited by 47 | Viewed by 8257

Abstract

Microwave-assisted solvent-free modification of pectin was successfully accomplished, consisting in the esterification of several fatty acids by pectin alcoholic functions. The reaction was performed by simply mixing the reagents with a catalytic amount of the inorganic base (potassium carbonate) and irradiating the obtained [...] Read more.

Microwave-assisted solvent-free modification of pectin was successfully accomplished, consisting in the esterification of several fatty acids by pectin alcoholic functions. The reaction was performed by simply mixing the reagents with a catalytic amount of the inorganic base (potassium carbonate) and irradiating the obtained mixture with microwaves for a short time (3–6 min). The replacement of the traditional heating with a microwave source allowed the development of a new synthetic protocol which provided increased yield of the final products, since it eliminates the small amount of degraded polysaccharide produced during traditional oil bath heating. The desired esters were fully characterized by FT-IR spectroscopy and thermogravimetric analysis. Full article

(This article belongs to the Special Issue Solvent-Free Synthesis)

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Open AccessArticle

Studies on 2-Arylhydrazononitriles: Synthesis of 3-Aryl-2-arylhydrazopropanenitriles and Their Utility as Precursors to 2-Substituted Indoles, 2-Substituted-1,2,3-Triazoles, and 1-Substituted Pyrazolo[4,3-d]pyrimidines

by Khaled D. Khalil and Hamad M. Al-Matar

Molecules 2012, 17(10), 12225-12233; https://doi.org/10.3390/molecules171012225 - 18 Oct 2012

Cited by 9 | Viewed by 6720

Abstract

Coupling of 2-benzylmalononitrile with aromatic diazonium salts afforded 3-phenyl-2-arylhydrazonopropanenitriles 4a,b, which were rearranged into 2-cyanoindoles 5a,b upon heating with ZnCl₂ in the presence of glacial acetic acid. The produced indole derivatives 5a,b can be successfully [...] Read more.

Coupling of 2-benzylmalononitrile with aromatic diazonium salts afforded 3-phenyl-2-arylhydrazonopropanenitriles 4a,b, which were rearranged into 2-cyanoindoles 5a,b upon heating with ZnCl₂ in the presence of glacial acetic acid. The produced indole derivatives 5a,b can be successfully used as valuable precursors to synthesize 1,2,4-oxadiazolylindoles 8a,b. The reaction of arylhydrazononitriles 4a,b with hydroxylamine afforded an amidoximes 9a,b that could be cyclized into 1,2,3-triazole-4-amines 10a,b. In addition, 4a,b could be converted into 4-aminopyrazoles 12a,b via condensation with chloroacetonitrile in the presence of triethylamine as a basic catalyst. Finally, compounds 12a,b were refluxed with dimethylformamide dimethylacetal (DMFDMA) to afford amidines 13a,b that were readily cyclized to the corresponding pyrazolo[4,3-d]pyrimidines 14a,b when refluxed with ammonium acetate. Full article

(This article belongs to the Section Organic Chemistry)

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Open AccessArticle

Discovery and Validation of SIRT2 Inhibitors Based on Tenovin-6: Use of a ¹H-NMR Method to Assess Deacetylase Activity

by Lisa Pirrie, Anna R. McCarthy, Louise L. Major, Vaida Morkūnaitė, Asta Zubrienė, Daumantas Matulis, Sonia Lain, Tomas Lebl and Nicholas J. Westwood

Molecules 2012, 17(10), 12206-12224; https://doi.org/10.3390/molecules171012206 - 18 Oct 2012

Cited by 10 | Viewed by 9385

Abstract

The search for potent and selective sirtuin inhibitors continues as chemical tools of this type are of use in helping to assign the function of this interesting class of deacetylases. Here we describe SAR studies starting from the unselective sirtuin inhibitor tenovin-6. These [...] Read more.

The search for potent and selective sirtuin inhibitors continues as chemical tools of this type are of use in helping to assign the function of this interesting class of deacetylases. Here we describe SAR studies starting from the unselective sirtuin inhibitor tenovin-6. These studies identify a sub-micromolar inhibitor that has increased selectivity for SIRT2 over SIRT1 compared to tenovin-6. In addition, a ¹H-NMR-based method is developed and used to validate further this class of sirtuin inhibitors. A thermal shift analysis of SIRT2 in the presence of tenovin-6, -43, a control tenovin and the known SIRT2 inhibitor AGK2 is also presented. Full article

(This article belongs to the Special Issue Chemical Genetics)

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Open AccessCommunication

Bioactive Oleanane, Lupane and Ursane Triterpene Acid Derivatives

by Maria De L. e Silva, Juceni P. David, Lidércia C. R. C. Silva, Rauldenis A. F. Santos, Jorge M. David, Luciano S. Lima, Pedro S. Reis and Renato Fontana

Molecules 2012, 17(10), 12197-12205; https://doi.org/10.3390/molecules171012197 - 17 Oct 2012

Cited by 53 | Viewed by 10472

Abstract

Betulinic, ursolic and oleanolic acids isolated from the aerial parts of Eriope blanchetii (Lamiaceae) were subjected to different esterification reactions, yielding 12 C-3 position ester derivatives. All compounds were identified using spectroscopic techniques, such as IR, ¹H-NMR and MS. The derivatives were [...] Read more.

Betulinic, ursolic and oleanolic acids isolated from the aerial parts of Eriope blanchetii (Lamiaceae) were subjected to different esterification reactions, yielding 12 C-3 position ester derivatives. All compounds were identified using spectroscopic techniques, such as IR, ¹H-NMR and MS. The derivatives were further investigated for their antioxidant level, Artemia salina lethality and antimicrobial activity. Full article

(This article belongs to the Special Issue Triterpenes and Triterpenoids 2013)

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Open AccessArticle

Synthesis and Herbicidal Activity of Substituted Pyrazole Isothiocyanates

by Hua Wu, Jun-Tao Feng, Kai-Chun Lin and Xing Zhang

Molecules 2012, 17(10), 12187-12196; https://doi.org/10.3390/molecules171012187 - 17 Oct 2012

Cited by 27 | Viewed by 6576

Abstract

Isothiocyanates and substituted pyrazoles were combined to form a series of novel isothiocyanates with highly effective herbicidal activity. The target compounds were analyzed by elemental analysis, ¹H-NMR, EI-MS and IR spectroscopy. The synthesized compounds, particularly compounds 3-1 and 3- [...] Read more.

Isothiocyanates and substituted pyrazoles were combined to form a series of novel isothiocyanates with highly effective herbicidal activity. The target compounds were analyzed by elemental analysis, ¹H-NMR, EI-MS and IR spectroscopy. The synthesized compounds, particularly compounds 3-1 and 3-7, exhibited good herbicidal activities against four weeds. The EC₅₀ values of compound 3-1 against Echinochloa crusgalli L., Cyperus iria L., Dactylis glomerata L., and Trifolium repens L. were 64.32, 65.83, 62.42, and 67.72 µg/mL, respectively. The EC₅₀ values of compound 3-7 against E. crusgalli L., C. iria L., D. glomerata L., T. repens L. were 65.33, 64.90, 59.41 and 67.41 µg/mL, respectively. Compounds 3-1 and 3-7 may be further optimized as lead compounds for new herbicides. Full article

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Open AccessReview

The Final Link: Tapping the Power of Chemical Genetics to Connect the Molecular and Biologic Functions of Mitotic Protein Kinases

by Robert F. Lera and Mark E. Burkard

Molecules 2012, 17(10), 12172-12186; https://doi.org/10.3390/molecules171012172 - 17 Oct 2012

Cited by 3 | Viewed by 8803

Abstract

During mitosis, protein kinases coordinate cellular reorganization and chromosome segregation to ensure accurate distribution of genetic information into daughter cells. Multiple protein kinases contribute to mitotic regulation, modulating molecular signaling more rapidly than possible with gene expression. However, a comprehensive understanding of how [...] Read more.

During mitosis, protein kinases coordinate cellular reorganization and chromosome segregation to ensure accurate distribution of genetic information into daughter cells. Multiple protein kinases contribute to mitotic regulation, modulating molecular signaling more rapidly than possible with gene expression. However, a comprehensive understanding of how kinases regulate mitotic progression remains elusive. The challenge arises from multiple functions and substrates, a large number of “bystander” phosphorylation events, and the brief window in which all mitotic events transpire. Analog-sensitive alleles of protein kinases are powerful chemical genetic tools for rapid and specific interrogation of kinase function. Moreover, combining these tools with advanced proteomics and substrate labeling has identified phosphorylation sites on numerous protein targets. Here, we review the chemical genetic tools available to study kinase function and identify substrates. We describe how chemical genetics can also be used to link kinase function with cognate phosphorylation events to provide mechanistic detail. This can be accomplished by dissecting subsets of kinase functions and chemical genetic complementation. We believe a complete “chemical genetic toolbox” will ultimately allow a comprehensive understanding of how protein kinases regulate mitosis. Full article

(This article belongs to the Special Issue Chemical Genetics)

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Open AccessArticle

Synthesis and Characterization of New Thieno[3,2-b]thiophene Derivatives

by Moawia O. Ahmed, Wojciech Pisula and Subodh G. Mhaisalkar

Molecules 2012, 17(10), 12163-12171; https://doi.org/10.3390/molecules171012163 - 16 Oct 2012

Cited by 18 | Viewed by 7879

Abstract

Three derivatives of thieno[3,2-b]thiophene end-capped with phenyl units have been synthesized and characterized by MALDI TOF mass spectroscopy, elemental analysis, UV-vis absorption spectroscopy and thermogravimetric analysis (TGA). All compounds were prepared using Pd-catalyzed Stille or Suzuki coupling reactions. Optical measurements and [...] Read more.

Three derivatives of thieno[3,2-b]thiophene end-capped with phenyl units have been synthesized and characterized by MALDI TOF mass spectroscopy, elemental analysis, UV-vis absorption spectroscopy and thermogravimetric analysis (TGA). All compounds were prepared using Pd-catalyzed Stille or Suzuki coupling reactions. Optical measurements and thermal analysis revealed that these compounds are promising candidates for p-type organic semiconductor applications. Full article

(This article belongs to the Special Issue Macromolecules: Chemistry, Medicinal and Functional Materials)

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234 KiB

Open AccessArticle

Side-chain Modifications of Highly Functionalized 3(2H)-Furanones

by Viviani Nardini, Shirley Muniz Machado Rodrigues, Maurício Gomes Constantino and Gil Valdo José da Silva

Molecules 2012, 17(10), 12151-12162; https://doi.org/10.3390/molecules171012151 - 16 Oct 2012

Cited by 6 | Viewed by 4774

Abstract

A series of 3(2H)-furanones, based on side-chain modifications of a parent 3(2H)-furanone, was synthesized in good yield. The parent compound was prepared by hydrogenolysis, and subsequent acid hydrolysis, of isoxazole derivatives. The isoxazole was prepared by a [3+2] 1,3-dipolar [...] Read more.

A series of 3(2H)-furanones, based on side-chain modifications of a parent 3(2H)-furanone, was synthesized in good yield. The parent compound was prepared by hydrogenolysis, and subsequent acid hydrolysis, of isoxazole derivatives. The isoxazole was prepared by a [3+2] 1,3-dipolar cycloaddition reaction between 3-butyn-2-ol and nitrile oxide. Full article

(This article belongs to the Section Organic Chemistry)

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Open AccessArticle

Synthesis and Field Evaluation of the Sex Pheromone Analogues to Soybean Pod Borer Leguminivora glycinivorella

by Dai-Hua Hu, Jun He, Yi-Wan Zhou, Jun-Tao Feng and Xing Zhang

Molecules 2012, 17(10), 12140-12150; https://doi.org/10.3390/molecules171012140 - 16 Oct 2012

Cited by 10 | Viewed by 7952

Abstract

In order to develop efficient lures for soybean pod borer Leguminivora glycinivorella (Matsumura) in China, (E,E)-8,10-dodecadienyl acetate (EE-8,10-12:Ac), the main component of the pheromone of L. glycinivorella, and 12 structurally-related compounds were synthesised in good overall yields, regiospecificities, [...] Read more.

In order to develop efficient lures for soybean pod borer Leguminivora glycinivorella (Matsumura) in China, (E,E)-8,10-dodecadienyl acetate (EE-8,10-12:Ac), the main component of the pheromone of L. glycinivorella, and 12 structurally-related compounds were synthesised in good overall yields, regiospecificities, and stereo-selectivities via coupling reactions catalysed by Li₂CuCl₄. The effect of different synthetic compounds, alone or in combination with EE-8,10-12:Ac, on numbers of captured L. glycinivorella males was evaluated. EE-8,10-12:Ac, (E)-10-dodecenyl acetate (E-10-12:Ac), (E)-8-dodecenol (E-8-12:OH), tetradecyl acetate (14:Ac), and (Z)-9-tetradecenyl acetate (Z-9-14:Ac) alone displayed different attractiveness to L. glycinivorella males. 14:Ac, E-8-12:OH, E-10-12:Ac, (E,E)-8,10-dodecadienal (EE-8,10-12:Ald), (E)-8-dodecenal (E-8-12:Ald), (E)-10-dodecenal (E-10-12:Ald) and Z-9-14:Ac all showed a synergistic effect to EE-8,10-12:Ac at certain dosages. The binary mixtures of EE-8,10-12:Ac and E-10-12:Ald, Z-9-14:Ac,14:Ac, E-8-12:Ald, EE-8,10-12:Ald, E-8-12:OH, or E-10-12:Ac in suitable ratios give 17.00-, 10.98-, 10.67-, 6.73-, 5.54-, 4.30- and 4.50-fold increases in trap catch, respectively, over the standard pheromone lure, and as novel pheromone blends, demonstrated potential use in pheromone traps to monitor or control L. glycinivorella populations in China. Full article

(This article belongs to the Section Organic Chemistry)

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Open AccessArticle

Suzuki-Miyaura Reactions Catalyzed by C₂-Symmetric Pd-Multi-Dentate N-Heterocyclic Carbene Complexes

by Lan Jiang, Fengjun Shan, Zhengning Li and Defeng Zhao

Molecules 2012, 17(10), 12121-12139; https://doi.org/10.3390/molecules171012121 - 16 Oct 2012

Cited by 15 | Viewed by 6697

Abstract

Suzuki-Miyaura coupling reactions are promoted by Pd complexes ligated with C₂-symmetric multi-dentate N-heterocyclic carbenes derived in situ from Pd(OAc)₂ and imidazolium salts. Good to excellent yields were obtained for aryl bromides as substrates. Turnover numbers of up to 10 [...] Read more.

Suzuki-Miyaura coupling reactions are promoted by Pd complexes ligated with C₂-symmetric multi-dentate N-heterocyclic carbenes derived in situ from Pd(OAc)₂ and imidazolium salts. Good to excellent yields were obtained for aryl bromides as substrates. Turnover numbers of up to 10⁵ could be achieved with 5 × 10⁻⁴ mol% of Pd(OAc)₂/1 × 10⁻³ mol% NHC precatalyst in 24 h. Full article

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Open AccessArticle

Acetylated and Methylated β-Cyclodextrins as Viable Soluble Supports for the Synthesis of Short 2′-Oligodeoxyribo-nucleotides in Solution

by Alejandro Gimenez Molina, Vyacheslav Kungurtsev, Pasi Virta and Harri Lönnberg

Molecules 2012, 17(10), 12102-12120; https://doi.org/10.3390/molecules171012102 - 16 Oct 2012

Cited by 21 | Viewed by 10366

Abstract

Novel soluble supports for oligonucleotide synthesis 11a–c have been prepared by immobilizing a 5′-O-protected 3′-O-(hex-5-ynoyl)thymidine (6 or 7) to peracetylated or permethylated 6-deoxy-6-azido-β-cyclodextrins 10a or 10b by Cu(I)-promoted 1,3-dipolar cycloaddition. The applicability of the supports [...] Read more.

Novel soluble supports for oligonucleotide synthesis 11a–c have been prepared by immobilizing a 5′-O-protected 3′-O-(hex-5-ynoyl)thymidine (6 or 7) to peracetylated or permethylated 6-deoxy-6-azido-β-cyclodextrins 10a or 10b by Cu(I)-promoted 1,3-dipolar cycloaddition. The applicability of the supports to oligonucleotide synthesis by the phosphoramidite strategy has been demonstrated by assembling a 3′-TTT-5′ trimer from commercially available 5′-O-(4,4′-dimethoxytrityl)thymidine 3′-phosphoramidite. To simplify the coupling cycle, the 5′-O-(4,4′-dimethoxytrityl) protecting group has been replaced with an acetal that upon acidolytic removal yields volatile products. For this purpose, 5′-O-(1-methoxy-1-methylethyl)-protected 3′-(2-cyanoethyl-N,N-diisopropyl-phosphoramidite)s of thymidine (5a), N⁴-benzoyl-2′-deoxycytidine (5b) and N⁶-benzoyl-2′-deoxyadenosine (5c) have been synthesized and utilized in synthesis of a pentameric oligonucleotide 3′-TTCAT-5′ on the permethylated cyclodextrin support 11c. Full article

(This article belongs to the Special Issue Nucleic Acid Analogs)

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c-IAP1 Binds and Processes PCSK9 Protein: Linking the c-IAP1 in a TNF-α Pathway to PCSK9-Mediated LDLR Degradation Pathway

by Weiming Xu, Lizhi Liu and David Hornby

Molecules 2012, 17(10), 12086-12101; https://doi.org/10.3390/molecules171012086 - 15 Oct 2012

Cited by 23 | Viewed by 12281

Abstract

Recent genetic studies have shown that PCSK9, one of the key genes in cholesterol metabolism, plays a critical role by controlling the level of low-density lipoprotein receptor. However, how PCSK9 mediates LDLR degradation is still unknown. By combining a shotgun proteomic method and [...] Read more.

Recent genetic studies have shown that PCSK9, one of the key genes in cholesterol metabolism, plays a critical role by controlling the level of low-density lipoprotein receptor. However, how PCSK9 mediates LDLR degradation is still unknown. By combining a shotgun proteomic method and differential analysis of natural occurring mutations of the PCSK9 gene, we found that an E3 ubiquitin ligase c-IAP1 binds and processes PCSK9 protein. One of the ‘gain-of-function’ mutations, S127R, is defective with respect to binding to c-IAP1, and thus has defective autocatalytic activity. Knockdown of c-IAP1 impairs PCSK9 processing and autocatalytic cleavage. In c-IAP1 null mouse embryonic fibroblasts (MEFs), there is a dramatic decrease in secreted mature PCSK9 protein accompanied by a significant increase in LDLR protein levels compared with matched wild-type MEF cells. c-IAP1 also acts as an E3 ligase for ubiquitination of PCSK9. Ubiquitin containing only lysine-27 mediated PCSK9 ubiquitination by c-IAP1. Given K27-linked polyubiquitination promotes lysosomal localization, the finding indicates the c-IAP1 acts on both secretion of PCSK9 and its lysosomal localization. The novel pathway described here will open new avenues for exploring novel disease treatments. Full article

(This article belongs to the Section Molecular Diversity)

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A Novel Class of Selective Acetylcholinesterase Inhibitors: Synthesis and Evaluation of (E)-2-(Benzo[d]thiazol-2-yl)-3-heteroarylacrylonitriles

by Pedro De la Torre, Luis Astudillo Saavedra, Julio Caballero, Jairo Quiroga, Jans H. Alzate-Morales, Margarita Gutiérrez Cabrera and Jorge Trilleras

Molecules 2012, 17(10), 12072-12085; https://doi.org/10.3390/molecules171012072 - 15 Oct 2012

Cited by 36 | Viewed by 8667

Abstract

(E)-2-(benzo[d]thiazol-2-yl)-3-heteroarylacrylonitriles are described as a new class of selective inhibitors of acetylcholinesterase (AChE). The most potent compound in the series exhibited good AChE inhibitory activity (IC₅₀ = 64 µM). Compound 7f was found to be more selective than [...] Read more.

(E)-2-(benzo[d]thiazol-2-yl)-3-heteroarylacrylonitriles are described as a new class of selective inhibitors of acetylcholinesterase (AChE). The most potent compound in the series exhibited good AChE inhibitory activity (IC₅₀ = 64 µM). Compound 7f was found to be more selective than galanthamine in inhibiting AChE and it showed a moderate selectivity index. Kinetic studies on AChE indicated that a competitive type of inhibition pattern exist for these acrylonitrile derivates. Molecular docking models of the ligand-AChE complexes suggest that compound 7g is located on the periphery of the AChE active site. Full article

(This article belongs to the Section Medicinal Chemistry)

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Molecules, Volume 17, Issue 10 (October 2012) – 84 articles , Pages 11294-12468

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