Background: Pharmacophore mapping and molecular docking can be synergistically integrated to impr... more Background: Pharmacophore mapping and molecular docking can be synergistically integrated to improve the drug design and discovery process. A rational strategy, combiphore approach, derived from the combined study of Structure and Ligand based pharmacophore has been described to identify novel GPR40 modulators. Methods: DISCOtech module from Discovery studio was used for the generation of the Structure and Ligand based pharmacophore models which gave hydrophobic aromatic, ring aromatic and negative ionizable as essential pharmacophoric features. The generated models were validated by screening active and inactive datasets, GH scoring and ROC curve analysis. The best model was exposed as a 3D query to screen the hits from databases like GLASS (GPCR-Ligand Association), GPCR SARfari and Mini-Maybridge. Various filters were applied to retrieve the hit molecules having good drug-like properties. A known protein structure of hGPR40 (pdb: 4PHU) having TAK-875 as ligand complex was used to...
Background: Human GPR40 receptor, also known as free fatty-acid receptor 1, is a Gprotein- couple... more Background: Human GPR40 receptor, also known as free fatty-acid receptor 1, is a Gprotein- coupled receptor that binds long chain free fatty acids to enhance glucose-dependent insulin secretion. In order to improve the resistance and efficacy, computational tools were applied to a series of 3-aryl-3-ethoxypropanoic acid derivatives. A relationship between the structure and biological activity of these compounds, was derived using a three-dimensional quantitative structure-activity relationship (3D-QSAR) study using CoMFA, CoMSIA and two-dimensional QSAR study using HQSAR methods. Methods: Building the 3D-QSAR models, CoMFA, CoMSIA and HQSAR were performed using Sybyl-X software. The ratio of training to test set was kept 70:30. For the generation of 3D-QSAR model three different alignments were used namely, distill, pharmacophore and docking based alignments. Molecular docking studies were carried out on designed molecules using the same software. Results: Among all the three method...
Background: Dipeptidyl Peptidase 4 (DPP 4) enzyme cleaves an incretin-based glucoregulatory hormo... more Background: Dipeptidyl Peptidase 4 (DPP 4) enzyme cleaves an incretin-based glucoregulatory hormone Glucagon Like Peptide -1 from N-terminal where penultimate amino acid is either alanine or proline. Several DPP 4 inhibitors, “gliptins”, are approved for the management of Type 2 Diabetes or are under clinical trial. In the present study, combined pharmacophore and docking-based virtual screening protocol were used for the identification of new hits from the Specs Database, which would inhibit DPP 4. Methods: The entire computational studies were performed using the Discovery Studio v. 4.1 software package, Pipeline Pilot v. 9.2 (Accelrys Inc.) and FRED v. 2.2.5 (OpenEye Scientific Software). Common feature pharmacophore model was generated from known DPP 4 inhibitors and validated by Receiver Operating curve analysis and GH-scoring method. Database search of Specs commercial database was performed using validated pharmacophore. Hits obtained from pharmacophore search were further do...
International Journal of Pharmaceutical Sciences and Drug Research
Glycogen synthase kinase-3β (GSK-3β) is an important class of therapeutic drug target currently r... more Glycogen synthase kinase-3β (GSK-3β) is an important class of therapeutic drug target currently receiving wide attention. In our computational approach, shape-based similarity search was used to screen the SPECS database, based on the shape of Tideglusib molecule; a known GSK-3β inhibitor. The resulting virtual hits were applied for docking studies on the known binding pockets of GSK-3β. A novel compound [7,10-dioxo-4,5-dihydro-7H,10H-pyrano[3,2,1-ij]quinolin-8-yl acetate] proposed from docking results in the substrate site of GSK-3β was found to have inhibitory activity (IC50) above 100μM concentration in ADP-GloTM Kinase assay. This communication aims to put forward in identifying newer hit on GSK-3β target via virtual screening approach.
Glycogen synthase kinase-3 (GSK-3) is a multitasking serine/threonine protein kinase, which is as... more Glycogen synthase kinase-3 (GSK-3) is a multitasking serine/threonine protein kinase, which is associated with the pathophysiology of several diseases such as diabetes, cancer, psychiatric and neurodegenerative diseases. Tideglusib is a potent, selective, and irreversible GSK-3 inhibitor that has been investigated in phase II clinical trials for the treatment of progressive supranuclear palsy and Alzheimer's disease. In the present study, we performed pharmacophore feature-based virtual screening for identifying potent targetspecific GSK-3 inhibitors. We found 64 compounds that show better GSK-3 binding potentials compared with those of Tideglusib. We further validated the obtained binding potentials by performing 20-ns molecular dynamics simulations for GSK-3 complexed with Tideglusib and with the best compound found via virtual screening in this study. Several interesting molecular-level interactions were identified, including a covalent interaction with Cys199 residue at the ...
Journal of Pharmaceutical and Biomedical Analysis, Apr 1, 2011
This work presents the isolation and characterization of the alkaline degradant of Ezetimibe. Eze... more This work presents the isolation and characterization of the alkaline degradant of Ezetimibe. Ezetimibe, a selective inhibitor of intestinal cholesterol absorption, was subjected to alkaline degradation. Ezetimibe was reacted with 0.1M methanolic sodium hydroxide solution for 10min at 80°C to yield alkaline degradant to an extent of 90% of initial amount of the drug taken. This degradant was detected by high performance liquid chromatography (HPLC) at relative retention time (RRT) of 1.48 with respect to Ezetimibe. HPLC method involved an isocratic elution on a Waters Symmetry C(8) 150mm×4.6mm, 5μm column using ammonium acetate buffer (pH 4.5, 50mM) - acetonitrile (50:50, v/v) as the mobile phase at a flow rate of 1.0mL/min and UV detection at 242nm. The degradant was isolated by preparative HPLC. Purity of the isolated solid was found to be more than 99%. Structure of alkaline degradant was confirmed by LC-MS, (1)H and (13)C NMR and IR spectroscopy. On the basis of spectral data, the structure of the degradant was confirmed as 5-(4-fluorophenyl)-2-[(4-fluorophenyl amino)-(4-hydroxyphenyl)methyl]-pent-4-enoic acid. The route for the formation of this degradant is also proposed. Determining the structures of degradation products arouse during stress testing can be useful for preclinical discovery efforts.
Eurasian Journal of Analytical Chemistry, Mar 10, 2010
Validated sensitive and highly selective stability indicating methods are adopted for simultaneou... more Validated sensitive and highly selective stability indicating methods are adopted for simultaneous quantitative determination of sulpiride and mebeverine hydrochloride in presence of their reported impurities and hydrolytic degradates whether in pure forms or in pharmaceutical formulation. The first method is High Performance Liquid Chromatography, where the mixture of sulpiride and mebeverine hydrochloride together with the reported interferents plus metopimazine as internal standard are separated on a reversed phase cyano column (5 microm ps, 250 mm x 4.6 id) using acetonitrile: water (70:30 v/v) adjusted to pH = 7 as a mobile phase. The drugs were detected at 221 nm over a concentration range of 5-40 microg ml(-1) and 5-60 microg ml(-1) with mean percentage recoveries 99.75% (S.D. 0.910) and 99.99% (S.D. 0.450) for sulpiride and mebeverine hydrochloride respectively. The second method is High Performance Thin Layer Chromatography, where sulpiride and mebeverine hydrochloride are separated on silica gel HPTLC F(254) plates using absolute ethanol:methylene chloride:triethyl amine (7:3:0.2 by volume) as mobile phase and scanning of the separated bands at 221 nm over a concentration range of 0.4-1.4 and 0.2-1.6 microg band(-1) with mean percentage recoveries 101.01% (S.D. 1.991) and 100.40% (S.D. 1.868) for sulpiride and mebeverine hydrochloride respectively.
Astaxanthin (3, 3'-dihydroxy-β, β-carotene-4, 4'-dione; AST) belongs to class of ... more Astaxanthin (3, 3'-dihydroxy-β, β-carotene-4, 4'-dione; AST) belongs to class of xanthophylls and is very effective antioxidant. It has very poor aqueous solubility resulting in lower bioavailability which presents major concerns in product development for oral use. AST was microencapsulated with soluble polymers using spray drying to improve its solubility and bioavailability. Quality by Design (QbD), a widely used approach for prediction of quality for desired specifications and effects was applied Design of Experiments (DOE), a useful component of QbD was utilized to understand the effect of variables and their interactions. Different formulation variables like ratio of hydrophilic carriers, concentration of solubilizers and homogenizer speed were challenged in the experimental design during the process of microencapsulation. The optimized formulation showed consistent release rate and characterization was done by DSC, XRD and SEM study. Percent cell growth inhibition was increased in optimized formulation as compared to plain AST. This QbD study can form a basis for further development of poorly water soluble AST formulation by oral route with improved bioavailability on larger scale.
Journal of Inclusion Phenomena and Macrocyclic Chemistry, 2015
ABSTRACT Lutein (LUT) is one of the most important carotenoids and; the most prominent being its ... more ABSTRACT Lutein (LUT) is one of the most important carotenoids and; the most prominent being its antioxidant activity. However, its use is limited due to poor solubility and instability under adverse conditions. An attempt is made to increase the solubility and hence bioavailability of LUT using various cyclodextrins viz., Betacyclodextrin (βCD), Hydroxypropyl Betacyclodextrin (HP-βCD) and Methyl Betacyclodextrin (M-βCD). Physical mixtures and Spray dried inclusion complexes were prepared and characterized using Spectroscopic techniques, DSC and XRD studies. From the phase solubility and dissolution studies it was found that, M-βCD significantly improved the solubility of LUT. These complexes were further subjected to in vitro anti-proliferative activity in order to validate results obtained from solubility studies. The biological results were in congruence with the results of solubility studies. Spray dried complex of LUT: M-βCD showed significant percent growth inhibition as compared to other two complexes and LUT alone. Molecular modeling studies established the host-guest stoichiometry with the lowest energy to be 2:1, with the two hexatomic rings of a LUT molecule occupying the two M-βCD cavities. The present study forms the basis for the development of oral formulations of LUT with significantly improved solubility and bioavailability.
The development of a new drug is a long and costly process. Determination of in vivo activity of ... more The development of a new drug is a long and costly process. Determination of in vivo activity of a natural drug with is also a challenging work. Reverse pharmacognosy aim toward finding of new biological targets for natural compounds by virtual or real screening and identifying natural resources that contain the active molecules. Reverse pharmacognosy utilizes techniques, such as high-throughput screening (HTS), virtual screening and a knowledge database containing the traditional uses of plants. Pharmacognosy uses plants to discover new bio-active compounds whereas Reverse Pharmacognosy uses natural chemicals to find new plant properties. Integrating pharmacognosy and reverse pharmacognosy in the research process may provide an efficient and rapid tool for natural drug discovery.
Journal of Inclusion Phenomena and Macrocyclic Chemistry, 2015
ABSTRACT Astaxanthin (AXT) is a commercially potential oxygenated carotenoid that has gained exte... more ABSTRACT Astaxanthin (AXT) is a commercially potential oxygenated carotenoid that has gained extensive acceptance as a nutritional ingredient in Nutraceuticals and food additives, however this bioactive fails to gather absolutesignificance due to poor aqueous solubility. This study explores the improved dissolution rate of AXT by complexation of AXT with methyl betacyclodextrin (M-βCD) using spray drying technique which is very much scalable and accepted in industry. The experimental methodology undertaken proved that at 1.0 molar concentrationsof M-βCD, the solubility of AXT was 0.012 mM, representing a54-fold enhancement over baseline solubility. A 10 fold increase in the dissolution rate was observed within 45 min in case of spray dried complex of AXT with M-βCD as compared to plain AXT. HepG2 cell line study provedthat AXT bio accessibility increases when complexed with M-βCD using spray drying technique. Also, these complexes were further characterized by FTIR, UV, DSC, 1H NMR, XRD and molecular modeling analysis. The results confirmed that the hexatomic side rings of the AXT molecule was partly incorporated into the M-βCD cavity. The present study provides the basis for the development of soluble andbioavailable oral formulations of AXT using cyclodextrin complexation by spray drying technology.
Drug-resistant bacteria are now a global health threat. In the last 5 years the WHO, The House of... more Drug-resistant bacteria are now a global health threat. In the last 5 years the WHO, The House of Lords (UK), the Centre for Disease Control (USA) and many more agencies have presented reports on the scale of this problem. Microorganisms multiply very rapidly and have adapted to fill almost every available environmental niche (Rapidly growing species of bacteria under ideal conditions of growth can multiply in about 20 minutes). All members of the chemically related beta-lactam class act at the same phase in cell wall synthesis; as a result, a bacterial cell resistant to one agent is often resistant to all other analogues. The beta-peptide has two promising characteristics that distinguish it from traditional antibiotics. Firstly, bacteria may have trouble developing resistance to the beta-peptide since bacterial defenses may not recognize its unnatural amino acids. Secondly, the magainins that the beta-peptides mimic have been around for millions of years, yet bacteria have not become resistant to them. All classes of antibiotics are subject to resistance by an efflux mechanism mediated by more than one type of pump within the same organism. The bacterial cell may have a membrane pump capable of pumping a class or several classes of antibacterial agents back out of the cell. Other mechanisms of drug resistance include destruction of beta-lactam ring by beta-lactamases, impermeability of the drug into the bacterial cell wall, alteration of targets within the bacterial cells and the by-pass mechanism (bacterial cell may have acquired an alternative mechanism for achieving the essential function).
Background: Pharmacophore mapping and molecular docking can be synergistically integrated to impr... more Background: Pharmacophore mapping and molecular docking can be synergistically integrated to improve the drug design and discovery process. A rational strategy, combiphore approach, derived from the combined study of Structure and Ligand based pharmacophore has been described to identify novel GPR40 modulators. Methods: DISCOtech module from Discovery studio was used for the generation of the Structure and Ligand based pharmacophore models which gave hydrophobic aromatic, ring aromatic and negative ionizable as essential pharmacophoric features. The generated models were validated by screening active and inactive datasets, GH scoring and ROC curve analysis. The best model was exposed as a 3D query to screen the hits from databases like GLASS (GPCR-Ligand Association), GPCR SARfari and Mini-Maybridge. Various filters were applied to retrieve the hit molecules having good drug-like properties. A known protein structure of hGPR40 (pdb: 4PHU) having TAK-875 as ligand complex was used to...
Background: Human GPR40 receptor, also known as free fatty-acid receptor 1, is a Gprotein- couple... more Background: Human GPR40 receptor, also known as free fatty-acid receptor 1, is a Gprotein- coupled receptor that binds long chain free fatty acids to enhance glucose-dependent insulin secretion. In order to improve the resistance and efficacy, computational tools were applied to a series of 3-aryl-3-ethoxypropanoic acid derivatives. A relationship between the structure and biological activity of these compounds, was derived using a three-dimensional quantitative structure-activity relationship (3D-QSAR) study using CoMFA, CoMSIA and two-dimensional QSAR study using HQSAR methods. Methods: Building the 3D-QSAR models, CoMFA, CoMSIA and HQSAR were performed using Sybyl-X software. The ratio of training to test set was kept 70:30. For the generation of 3D-QSAR model three different alignments were used namely, distill, pharmacophore and docking based alignments. Molecular docking studies were carried out on designed molecules using the same software. Results: Among all the three method...
Background: Dipeptidyl Peptidase 4 (DPP 4) enzyme cleaves an incretin-based glucoregulatory hormo... more Background: Dipeptidyl Peptidase 4 (DPP 4) enzyme cleaves an incretin-based glucoregulatory hormone Glucagon Like Peptide -1 from N-terminal where penultimate amino acid is either alanine or proline. Several DPP 4 inhibitors, “gliptins”, are approved for the management of Type 2 Diabetes or are under clinical trial. In the present study, combined pharmacophore and docking-based virtual screening protocol were used for the identification of new hits from the Specs Database, which would inhibit DPP 4. Methods: The entire computational studies were performed using the Discovery Studio v. 4.1 software package, Pipeline Pilot v. 9.2 (Accelrys Inc.) and FRED v. 2.2.5 (OpenEye Scientific Software). Common feature pharmacophore model was generated from known DPP 4 inhibitors and validated by Receiver Operating curve analysis and GH-scoring method. Database search of Specs commercial database was performed using validated pharmacophore. Hits obtained from pharmacophore search were further do...
International Journal of Pharmaceutical Sciences and Drug Research
Glycogen synthase kinase-3β (GSK-3β) is an important class of therapeutic drug target currently r... more Glycogen synthase kinase-3β (GSK-3β) is an important class of therapeutic drug target currently receiving wide attention. In our computational approach, shape-based similarity search was used to screen the SPECS database, based on the shape of Tideglusib molecule; a known GSK-3β inhibitor. The resulting virtual hits were applied for docking studies on the known binding pockets of GSK-3β. A novel compound [7,10-dioxo-4,5-dihydro-7H,10H-pyrano[3,2,1-ij]quinolin-8-yl acetate] proposed from docking results in the substrate site of GSK-3β was found to have inhibitory activity (IC50) above 100μM concentration in ADP-GloTM Kinase assay. This communication aims to put forward in identifying newer hit on GSK-3β target via virtual screening approach.
Glycogen synthase kinase-3 (GSK-3) is a multitasking serine/threonine protein kinase, which is as... more Glycogen synthase kinase-3 (GSK-3) is a multitasking serine/threonine protein kinase, which is associated with the pathophysiology of several diseases such as diabetes, cancer, psychiatric and neurodegenerative diseases. Tideglusib is a potent, selective, and irreversible GSK-3 inhibitor that has been investigated in phase II clinical trials for the treatment of progressive supranuclear palsy and Alzheimer's disease. In the present study, we performed pharmacophore feature-based virtual screening for identifying potent targetspecific GSK-3 inhibitors. We found 64 compounds that show better GSK-3 binding potentials compared with those of Tideglusib. We further validated the obtained binding potentials by performing 20-ns molecular dynamics simulations for GSK-3 complexed with Tideglusib and with the best compound found via virtual screening in this study. Several interesting molecular-level interactions were identified, including a covalent interaction with Cys199 residue at the ...
Journal of Pharmaceutical and Biomedical Analysis, Apr 1, 2011
This work presents the isolation and characterization of the alkaline degradant of Ezetimibe. Eze... more This work presents the isolation and characterization of the alkaline degradant of Ezetimibe. Ezetimibe, a selective inhibitor of intestinal cholesterol absorption, was subjected to alkaline degradation. Ezetimibe was reacted with 0.1M methanolic sodium hydroxide solution for 10min at 80°C to yield alkaline degradant to an extent of 90% of initial amount of the drug taken. This degradant was detected by high performance liquid chromatography (HPLC) at relative retention time (RRT) of 1.48 with respect to Ezetimibe. HPLC method involved an isocratic elution on a Waters Symmetry C(8) 150mm×4.6mm, 5μm column using ammonium acetate buffer (pH 4.5, 50mM) - acetonitrile (50:50, v/v) as the mobile phase at a flow rate of 1.0mL/min and UV detection at 242nm. The degradant was isolated by preparative HPLC. Purity of the isolated solid was found to be more than 99%. Structure of alkaline degradant was confirmed by LC-MS, (1)H and (13)C NMR and IR spectroscopy. On the basis of spectral data, the structure of the degradant was confirmed as 5-(4-fluorophenyl)-2-[(4-fluorophenyl amino)-(4-hydroxyphenyl)methyl]-pent-4-enoic acid. The route for the formation of this degradant is also proposed. Determining the structures of degradation products arouse during stress testing can be useful for preclinical discovery efforts.
Eurasian Journal of Analytical Chemistry, Mar 10, 2010
Validated sensitive and highly selective stability indicating methods are adopted for simultaneou... more Validated sensitive and highly selective stability indicating methods are adopted for simultaneous quantitative determination of sulpiride and mebeverine hydrochloride in presence of their reported impurities and hydrolytic degradates whether in pure forms or in pharmaceutical formulation. The first method is High Performance Liquid Chromatography, where the mixture of sulpiride and mebeverine hydrochloride together with the reported interferents plus metopimazine as internal standard are separated on a reversed phase cyano column (5 microm ps, 250 mm x 4.6 id) using acetonitrile: water (70:30 v/v) adjusted to pH = 7 as a mobile phase. The drugs were detected at 221 nm over a concentration range of 5-40 microg ml(-1) and 5-60 microg ml(-1) with mean percentage recoveries 99.75% (S.D. 0.910) and 99.99% (S.D. 0.450) for sulpiride and mebeverine hydrochloride respectively. The second method is High Performance Thin Layer Chromatography, where sulpiride and mebeverine hydrochloride are separated on silica gel HPTLC F(254) plates using absolute ethanol:methylene chloride:triethyl amine (7:3:0.2 by volume) as mobile phase and scanning of the separated bands at 221 nm over a concentration range of 0.4-1.4 and 0.2-1.6 microg band(-1) with mean percentage recoveries 101.01% (S.D. 1.991) and 100.40% (S.D. 1.868) for sulpiride and mebeverine hydrochloride respectively.
Astaxanthin (3, 3'-dihydroxy-β, β-carotene-4, 4'-dione; AST) belongs to class of ... more Astaxanthin (3, 3'-dihydroxy-β, β-carotene-4, 4'-dione; AST) belongs to class of xanthophylls and is very effective antioxidant. It has very poor aqueous solubility resulting in lower bioavailability which presents major concerns in product development for oral use. AST was microencapsulated with soluble polymers using spray drying to improve its solubility and bioavailability. Quality by Design (QbD), a widely used approach for prediction of quality for desired specifications and effects was applied Design of Experiments (DOE), a useful component of QbD was utilized to understand the effect of variables and their interactions. Different formulation variables like ratio of hydrophilic carriers, concentration of solubilizers and homogenizer speed were challenged in the experimental design during the process of microencapsulation. The optimized formulation showed consistent release rate and characterization was done by DSC, XRD and SEM study. Percent cell growth inhibition was increased in optimized formulation as compared to plain AST. This QbD study can form a basis for further development of poorly water soluble AST formulation by oral route with improved bioavailability on larger scale.
Journal of Inclusion Phenomena and Macrocyclic Chemistry, 2015
ABSTRACT Lutein (LUT) is one of the most important carotenoids and; the most prominent being its ... more ABSTRACT Lutein (LUT) is one of the most important carotenoids and; the most prominent being its antioxidant activity. However, its use is limited due to poor solubility and instability under adverse conditions. An attempt is made to increase the solubility and hence bioavailability of LUT using various cyclodextrins viz., Betacyclodextrin (βCD), Hydroxypropyl Betacyclodextrin (HP-βCD) and Methyl Betacyclodextrin (M-βCD). Physical mixtures and Spray dried inclusion complexes were prepared and characterized using Spectroscopic techniques, DSC and XRD studies. From the phase solubility and dissolution studies it was found that, M-βCD significantly improved the solubility of LUT. These complexes were further subjected to in vitro anti-proliferative activity in order to validate results obtained from solubility studies. The biological results were in congruence with the results of solubility studies. Spray dried complex of LUT: M-βCD showed significant percent growth inhibition as compared to other two complexes and LUT alone. Molecular modeling studies established the host-guest stoichiometry with the lowest energy to be 2:1, with the two hexatomic rings of a LUT molecule occupying the two M-βCD cavities. The present study forms the basis for the development of oral formulations of LUT with significantly improved solubility and bioavailability.
The development of a new drug is a long and costly process. Determination of in vivo activity of ... more The development of a new drug is a long and costly process. Determination of in vivo activity of a natural drug with is also a challenging work. Reverse pharmacognosy aim toward finding of new biological targets for natural compounds by virtual or real screening and identifying natural resources that contain the active molecules. Reverse pharmacognosy utilizes techniques, such as high-throughput screening (HTS), virtual screening and a knowledge database containing the traditional uses of plants. Pharmacognosy uses plants to discover new bio-active compounds whereas Reverse Pharmacognosy uses natural chemicals to find new plant properties. Integrating pharmacognosy and reverse pharmacognosy in the research process may provide an efficient and rapid tool for natural drug discovery.
Journal of Inclusion Phenomena and Macrocyclic Chemistry, 2015
ABSTRACT Astaxanthin (AXT) is a commercially potential oxygenated carotenoid that has gained exte... more ABSTRACT Astaxanthin (AXT) is a commercially potential oxygenated carotenoid that has gained extensive acceptance as a nutritional ingredient in Nutraceuticals and food additives, however this bioactive fails to gather absolutesignificance due to poor aqueous solubility. This study explores the improved dissolution rate of AXT by complexation of AXT with methyl betacyclodextrin (M-βCD) using spray drying technique which is very much scalable and accepted in industry. The experimental methodology undertaken proved that at 1.0 molar concentrationsof M-βCD, the solubility of AXT was 0.012 mM, representing a54-fold enhancement over baseline solubility. A 10 fold increase in the dissolution rate was observed within 45 min in case of spray dried complex of AXT with M-βCD as compared to plain AXT. HepG2 cell line study provedthat AXT bio accessibility increases when complexed with M-βCD using spray drying technique. Also, these complexes were further characterized by FTIR, UV, DSC, 1H NMR, XRD and molecular modeling analysis. The results confirmed that the hexatomic side rings of the AXT molecule was partly incorporated into the M-βCD cavity. The present study provides the basis for the development of soluble andbioavailable oral formulations of AXT using cyclodextrin complexation by spray drying technology.
Drug-resistant bacteria are now a global health threat. In the last 5 years the WHO, The House of... more Drug-resistant bacteria are now a global health threat. In the last 5 years the WHO, The House of Lords (UK), the Centre for Disease Control (USA) and many more agencies have presented reports on the scale of this problem. Microorganisms multiply very rapidly and have adapted to fill almost every available environmental niche (Rapidly growing species of bacteria under ideal conditions of growth can multiply in about 20 minutes). All members of the chemically related beta-lactam class act at the same phase in cell wall synthesis; as a result, a bacterial cell resistant to one agent is often resistant to all other analogues. The beta-peptide has two promising characteristics that distinguish it from traditional antibiotics. Firstly, bacteria may have trouble developing resistance to the beta-peptide since bacterial defenses may not recognize its unnatural amino acids. Secondly, the magainins that the beta-peptides mimic have been around for millions of years, yet bacteria have not become resistant to them. All classes of antibiotics are subject to resistance by an efflux mechanism mediated by more than one type of pump within the same organism. The bacterial cell may have a membrane pump capable of pumping a class or several classes of antibacterial agents back out of the cell. Other mechanisms of drug resistance include destruction of beta-lactam ring by beta-lactamases, impermeability of the drug into the bacterial cell wall, alteration of targets within the bacterial cells and the by-pass mechanism (bacterial cell may have acquired an alternative mechanism for achieving the essential function).
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Papers by Anuradha Gajjar