Positron emission tomography (PET) is rapidly emerging as the functional imaging method of choice... more Positron emission tomography (PET) is rapidly emerging as the functional imaging method of choice for in vivo imaging applications in a number of key areas of drug discovery and clinical pathology, but especially in oncology. One key limitation of PET is the requirement for rapid synthesis and purification of biomarker/drug molecules regiospecifically labelled with short-lived positron-emitting isotopes. In this review, we focus on the role of (18)F-labelled molecules in PET, presenting a perspective on the challenges associated with the synthesis and future clinical utility of a range of labelled small molecules and macromolecular structures. Further preclinical method development for the regiospecific synthesis of fluorinated biomarkers under mild conditions is required before a wide range of (18)F-labelled molecules take their place alongside clinically established oncology biomarkers such as (18)FDG and (18)FLT. In this review, we offer insights into current and future chemical methods for the efficient synthesis of fluorinated PET biomarkers, featuring modern technologies such as microwave-promoted chemistries and microfluidic reactors, both of which possess the capability to routinely and rapidly produce the small quantities of PET-labelled molecules under the mild and efficient conditions that are required for PET tracer synthesis. (18)F PET is a flourishing field with many applications in drug discovery and development, through radiolabelling of drug molecules or use of fluorinated disease biomarkers.
Muntingia calabura L. is a tropical plant species that belongs to the Elaeocarpaceae family. The ... more Muntingia calabura L. is a tropical plant species that belongs to the Elaeocarpaceae family. The present study is aimed at determining the hepatoprotective activity of methanol extract of M. calabura leaves (MEMC) using two models of liver injury in rats. Rats were divided into five groups (n=6) and received 10% DMSO (negative control), 50 mg/kg N-acetylcysteine (NAC; positive control), or MEMC (50, 250, and 500 mg/kg) orally once daily for 7 days and on the 8th day were subjected to the hepatotoxic induction using paracetamol (PCM). The blood and liver tissues were collected and subjected to biochemical and microscopical analysis. The extract was also subjected to antioxidant study using the 2,2-diphenyl-1-picrylhydrazyl-(DPPH) and superoxide anion-radical scavenging assays. At the same time, oxygen radical antioxidant capacity (ORAC) and total phenolic content were also determined. From the histological observation, lymphocyte infiltration and marked necrosis were observed in PCM-...
European journal of medicinal chemistry, Oct 1, 2012
A series of novel indole-containing diarylisoxazoles has been synthesised, based on our previous ... more A series of novel indole-containing diarylisoxazoles has been synthesised, based on our previous work on the synthesis and pro-apoptotic antitumour activity of indole-based diaryl 1,2,4-oxadiazoles. Concise synthetic routes to both 3-(indol-2-yl)-5-phenylisoxazoles and 5-(indol-2-yl)-3-phenylisoxazoles have been developed with full regiochemical control, bearing substituents on the indole ring, indole nitrogen, and/or phenyl group. Additionally a series of the related 5-(1H-indol-5-yl)-3-phenylisoxazoles has been prepared. In vitro evaluation in human cancer cell lines Colo320 (colon) and Calu-3 (lung) revealed preferential antiproliferative activity within the 5-(indol-5-yl)-3-phenylisoxazole series (low micromolar IC(50)). Further analysis revealed the ability of the indol-5-yl series to induce expression of effector caspases-3 and -7, and retention of viability of the human bronchial smooth muscle cell (BSMC) control cell population (particularly for compounds 18c and 18e).
With the growing number of population suffering of gastro-related diseases such as ulcer and gast... more With the growing number of population suffering of gastro-related diseases such as ulcer and gastritis, the need to find novel halal pharmaceutical ingredients with gastroprotective activity is also increasing significantly, especially among the Muslim population. The conventional antiulcer drugs are over shaded with unwanted side effects. Plant kingdom is regarded as one of the valuable source to fulfill such need. One of the plants that currently caught our attention is Sapium indicum. Therefore, based on the traditional use of S. indicum to relieve pain and to heal wound, as well as the scientifically reported antimicrobial, antinociceptive and antioxidant properties, this study was intended to evaluate the antiulcer potential of S.indcium aqueous extract (SIAE) using established ethanol and indomethacine-induced models, followed by pylorus ligation model for antiulcer mechanisms. The SIAE was prepared at doses of 25, 125 and 250 mg/kg, together with distilled water (negative con...
African Journal of Pharmacy and Pharmacology, 2013
The present study was carried out to elucidate the chemopreventive potential of methanol extract ... more The present study was carried out to elucidate the chemopreventive potential of methanol extract of Dicranopteris linearis (MEDL) in a two-stage mouse skin carcinogenesis model due to the interrelated inflammation, oxidative stress and tumor promotion pathways. MEDL was prepared in a dose range of 30 to 300 mg/kg body weight. A total of 48 imprinting control region (ICR) female mice (6 to 8 weeks old) were randomly assorted into six groups. To induce skin tumor formation, a single topical application of 7,12-dimethylbenz[a]anthracene (DMBA) at 100 μg/100 μl was applied to the shaved dorsal region of mice, followed by repetitive administration of 1% croton oil, twice weekly for 15 weeks. Topical application of MEDL, 30 min prior to the croton oil application significantly reduced the tumor incidence to 12.5% in 300 mg/kg MEDL-treated group as compared to 87.5% in carcinogen control. The latency period of tumor formation was increased from sixth week in the carcinogen control to ninth...
Channastriatus (Haruan), a freshwater and snakehead fish, is traditionally used by the Malay to h... more Channastriatus (Haruan), a freshwater and snakehead fish, is traditionally used by the Malay to heal wound and lessens post-operative pain and discomfort. The objective of the present study is to elucidate the gastroprotective activity of chloroform:metanol extract of C. striatus fillet. The fillets were extracted using the methanol: chloroform (2:1; v/v) solvent system. The extract (labeled as MCECS), prepared in the doses of 50, 250, and 500 mg/kg, was orally administered into rats for 7 continuous days and then the animals were subjected to the ethanol- and indomethacin-induced gastric ulcer models. Following the euthanization of treated rats, the stomach was callected for macroscopic and microscopic analysis. The results showed that oral administration of MCECS exhibited significant (p<0.05) and dose-dependent antiulcer activity when assessed using both models of gastric ulcer. In addition, the macroscopic findings were supported by the microscopic observations. In conclusion...
Muntingia calabura (M. calabura), locally known as "kerukup siam" or "buah ceri&qu... more Muntingia calabura (M. calabura), locally known as "kerukup siam" or "buah ceri" belongs to the family Muntingiaceae and has been scientifically demonstrated to exert various pharmacological activities. The objectives of the current study are to evaluate the antioxidant activities and to determine the subchronic toxicity of 90 days orally-administered methanol extract of M. calabura (MEMC) in male Sprague Dawley rats. The rats were randomly divided into four groups (n=6). Vehicle control received 8% tween 80 and treatment group received 50, 250 and 500 mg/kg of MEMC orally administered daily for 90 days. Blood collection was carried out to obtain the hematological and biochemical profile of the rats. The organs harvested were subjected to histopathological analysis. For the antioxidant test, the extract was subjected to antioxidant study using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH)- and superoxide anion-radical scavenging activity, total phenolic content (TPC)...
BACKGROUND: Eventhough 6-Mercaptopurine act as a major drug for rheumatoid arthritis (RA) treatme... more BACKGROUND: Eventhough 6-Mercaptopurine act as a major drug for rheumatoid arthritis (RA) treatment, however, its toxicity become a limitation. Therefore, this current study investigated whether 6-hydroxy-2-mercaptopurine (6H2MP) and 6-thioguanine (6TG) compounds are purine nucleoside analogues as a potential treatment of RA. The objective was to evaluate the therapeutics effects, especially the anti-inflammatory potential of 6H2MP and 6TG in the lipopolysaccharides (LPS)-induced RAW264.7 cells and phorbol myristate acetate (PMA)-induced HIG-82 cells.METHODS: Macrophage cells (RAW264.7) and rabbit synoviocytes (HIG-82) cells were induced using LPS and PMA to evaluate the anti-inflammatory potential of 6H2MP and 6TG. The cytotoxicity assessment was done by using MTT assay, while enzyme-linked immunosorbent assay (ELISA) was used to determine the anti‑inflammatory potential, including tumour necrosis factor (TNF-α), interleukins (IL-1β, and IL-6).RESULTS: Upon LPS-induced, RAW 264.7 m...
Positron emission tomography (PET) is rapidly emerging as the functional imaging method of choice... more Positron emission tomography (PET) is rapidly emerging as the functional imaging method of choice for in vivo imaging applications in a number of key areas of drug discovery and clinical pathology, but especially in oncology. One key limitation of PET is the requirement for rapid synthesis and purification of biomarker/drug molecules regiospecifically labelled with short-lived positron-emitting isotopes. In this review, we focus on the role of (18)F-labelled molecules in PET, presenting a perspective on the challenges associated with the synthesis and future clinical utility of a range of labelled small molecules and macromolecular structures. Further preclinical method development for the regiospecific synthesis of fluorinated biomarkers under mild conditions is required before a wide range of (18)F-labelled molecules take their place alongside clinically established oncology biomarkers such as (18)FDG and (18)FLT. In this review, we offer insights into current and future chemical methods for the efficient synthesis of fluorinated PET biomarkers, featuring modern technologies such as microwave-promoted chemistries and microfluidic reactors, both of which possess the capability to routinely and rapidly produce the small quantities of PET-labelled molecules under the mild and efficient conditions that are required for PET tracer synthesis. (18)F PET is a flourishing field with many applications in drug discovery and development, through radiolabelling of drug molecules or use of fluorinated disease biomarkers.
Muntingia calabura L. is a tropical plant species that belongs to the Elaeocarpaceae family. The ... more Muntingia calabura L. is a tropical plant species that belongs to the Elaeocarpaceae family. The present study is aimed at determining the hepatoprotective activity of methanol extract of M. calabura leaves (MEMC) using two models of liver injury in rats. Rats were divided into five groups (n=6) and received 10% DMSO (negative control), 50 mg/kg N-acetylcysteine (NAC; positive control), or MEMC (50, 250, and 500 mg/kg) orally once daily for 7 days and on the 8th day were subjected to the hepatotoxic induction using paracetamol (PCM). The blood and liver tissues were collected and subjected to biochemical and microscopical analysis. The extract was also subjected to antioxidant study using the 2,2-diphenyl-1-picrylhydrazyl-(DPPH) and superoxide anion-radical scavenging assays. At the same time, oxygen radical antioxidant capacity (ORAC) and total phenolic content were also determined. From the histological observation, lymphocyte infiltration and marked necrosis were observed in PCM-...
European journal of medicinal chemistry, Oct 1, 2012
A series of novel indole-containing diarylisoxazoles has been synthesised, based on our previous ... more A series of novel indole-containing diarylisoxazoles has been synthesised, based on our previous work on the synthesis and pro-apoptotic antitumour activity of indole-based diaryl 1,2,4-oxadiazoles. Concise synthetic routes to both 3-(indol-2-yl)-5-phenylisoxazoles and 5-(indol-2-yl)-3-phenylisoxazoles have been developed with full regiochemical control, bearing substituents on the indole ring, indole nitrogen, and/or phenyl group. Additionally a series of the related 5-(1H-indol-5-yl)-3-phenylisoxazoles has been prepared. In vitro evaluation in human cancer cell lines Colo320 (colon) and Calu-3 (lung) revealed preferential antiproliferative activity within the 5-(indol-5-yl)-3-phenylisoxazole series (low micromolar IC(50)). Further analysis revealed the ability of the indol-5-yl series to induce expression of effector caspases-3 and -7, and retention of viability of the human bronchial smooth muscle cell (BSMC) control cell population (particularly for compounds 18c and 18e).
With the growing number of population suffering of gastro-related diseases such as ulcer and gast... more With the growing number of population suffering of gastro-related diseases such as ulcer and gastritis, the need to find novel halal pharmaceutical ingredients with gastroprotective activity is also increasing significantly, especially among the Muslim population. The conventional antiulcer drugs are over shaded with unwanted side effects. Plant kingdom is regarded as one of the valuable source to fulfill such need. One of the plants that currently caught our attention is Sapium indicum. Therefore, based on the traditional use of S. indicum to relieve pain and to heal wound, as well as the scientifically reported antimicrobial, antinociceptive and antioxidant properties, this study was intended to evaluate the antiulcer potential of S.indcium aqueous extract (SIAE) using established ethanol and indomethacine-induced models, followed by pylorus ligation model for antiulcer mechanisms. The SIAE was prepared at doses of 25, 125 and 250 mg/kg, together with distilled water (negative con...
African Journal of Pharmacy and Pharmacology, 2013
The present study was carried out to elucidate the chemopreventive potential of methanol extract ... more The present study was carried out to elucidate the chemopreventive potential of methanol extract of Dicranopteris linearis (MEDL) in a two-stage mouse skin carcinogenesis model due to the interrelated inflammation, oxidative stress and tumor promotion pathways. MEDL was prepared in a dose range of 30 to 300 mg/kg body weight. A total of 48 imprinting control region (ICR) female mice (6 to 8 weeks old) were randomly assorted into six groups. To induce skin tumor formation, a single topical application of 7,12-dimethylbenz[a]anthracene (DMBA) at 100 μg/100 μl was applied to the shaved dorsal region of mice, followed by repetitive administration of 1% croton oil, twice weekly for 15 weeks. Topical application of MEDL, 30 min prior to the croton oil application significantly reduced the tumor incidence to 12.5% in 300 mg/kg MEDL-treated group as compared to 87.5% in carcinogen control. The latency period of tumor formation was increased from sixth week in the carcinogen control to ninth...
Channastriatus (Haruan), a freshwater and snakehead fish, is traditionally used by the Malay to h... more Channastriatus (Haruan), a freshwater and snakehead fish, is traditionally used by the Malay to heal wound and lessens post-operative pain and discomfort. The objective of the present study is to elucidate the gastroprotective activity of chloroform:metanol extract of C. striatus fillet. The fillets were extracted using the methanol: chloroform (2:1; v/v) solvent system. The extract (labeled as MCECS), prepared in the doses of 50, 250, and 500 mg/kg, was orally administered into rats for 7 continuous days and then the animals were subjected to the ethanol- and indomethacin-induced gastric ulcer models. Following the euthanization of treated rats, the stomach was callected for macroscopic and microscopic analysis. The results showed that oral administration of MCECS exhibited significant (p<0.05) and dose-dependent antiulcer activity when assessed using both models of gastric ulcer. In addition, the macroscopic findings were supported by the microscopic observations. In conclusion...
Muntingia calabura (M. calabura), locally known as "kerukup siam" or "buah ceri&qu... more Muntingia calabura (M. calabura), locally known as "kerukup siam" or "buah ceri" belongs to the family Muntingiaceae and has been scientifically demonstrated to exert various pharmacological activities. The objectives of the current study are to evaluate the antioxidant activities and to determine the subchronic toxicity of 90 days orally-administered methanol extract of M. calabura (MEMC) in male Sprague Dawley rats. The rats were randomly divided into four groups (n=6). Vehicle control received 8% tween 80 and treatment group received 50, 250 and 500 mg/kg of MEMC orally administered daily for 90 days. Blood collection was carried out to obtain the hematological and biochemical profile of the rats. The organs harvested were subjected to histopathological analysis. For the antioxidant test, the extract was subjected to antioxidant study using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH)- and superoxide anion-radical scavenging activity, total phenolic content (TPC)...
BACKGROUND: Eventhough 6-Mercaptopurine act as a major drug for rheumatoid arthritis (RA) treatme... more BACKGROUND: Eventhough 6-Mercaptopurine act as a major drug for rheumatoid arthritis (RA) treatment, however, its toxicity become a limitation. Therefore, this current study investigated whether 6-hydroxy-2-mercaptopurine (6H2MP) and 6-thioguanine (6TG) compounds are purine nucleoside analogues as a potential treatment of RA. The objective was to evaluate the therapeutics effects, especially the anti-inflammatory potential of 6H2MP and 6TG in the lipopolysaccharides (LPS)-induced RAW264.7 cells and phorbol myristate acetate (PMA)-induced HIG-82 cells.METHODS: Macrophage cells (RAW264.7) and rabbit synoviocytes (HIG-82) cells were induced using LPS and PMA to evaluate the anti-inflammatory potential of 6H2MP and 6TG. The cytotoxicity assessment was done by using MTT assay, while enzyme-linked immunosorbent assay (ELISA) was used to determine the anti‑inflammatory potential, including tumour necrosis factor (TNF-α), interleukins (IL-1β, and IL-6).RESULTS: Upon LPS-induced, RAW 264.7 m...
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