Mohammad Mahboob Alam

Thiazolidine-2,4-diones derivatives as PPAR-γ agonists: synthesis, molecular docking, in vitro and in vivo antidiabetic activity with hepatotoxicity risk evaluation and effect on PPAR-γ gene expression.

A library of conjugates of chromones and 2,4-thiazolidinedione has been synthesized by Knoevenagel condensation followed by reduction using hydrogen gas and Pd/C as a catalyst. Compounds 5c and 5e were most effective in lowering the blood glucose level comparable to standard drug pioglitazone. Compound 5e exhibited potent PPAR-γ transactivation of 48.72% in comparison to pioglitazone (62.48%). All the molecules showed good glide score against the PPAR-γ target in molecular docking study. PPAR-γ gene expression was significantly increased by compound 5e (2.56-fold) in comparison to standard drug pioglitazone. Compounds 5e and 5c did not cause any damage to the liver and may be considered as promising candidates for the development of new antidiabetic agents.

Anti-inflammatory and anti-nociceptive activities of ethanolic extract and its various fractions from Adiantum capillus veneris Linn.

AIM OF THE STUDY To investigate the anti-inflammatory and anti-nociceptive activities of the crude ethanolic extract of Adiantum capillus veneris Linn. (Adiantaceae) and its various fractions. MATERIALS AND METHODS The ethanolic extract and its fractions were given at a dose of 200 mg/kg po and 300 mg/kg po for testing their anti-inflammatory activity by carrageenan induced hind paw edema. The analgesic activity of the ethanolic extract and its fractions has been carried out by tail-flick method and writhing test at a dosage of 300 mg/kg po. Gastric ulceration studies have been further carried out to study the antiulcer effect of the ethanolic extract and its various fractions at dose of 900 mg/kg body weight. RESULTS Amongst the tested fractions, the ethyl acetate fraction exhibited better inhibition (67.27%) at 300 mg/kg po dosage when compared to the standard drug Indomethacin (63.63%) after 3h in the carrageenan induced hind paw edema. The anti-inflammatory activity of the ethanolic extract and its various fractions appear to be related to the inhibition of NO release, and the decreasing TNF-α level. The ethanolic extract and all its fractions especially the ethyl acetate (p<0.01) showed significant analgesic activity with insignificant ulceration as compared to the standard drug, i.e. ibuprofen. The histopathological study of ethanolic extract and its fractions reveals that none of them cause ulcer. CONCLUSION The present study indicates that Adiantum capillus veneris Linn. has significant anti-inflammatory and analgesic effect.

Design, synthesis, in silico molecular docking and biological evaluation of novel oxadiazole based thiazolidine-2,4-diones bis-heterocycles as PPAR-γ agonists.

A library of novel 1,3,4-oxadiazole and 2-4-thiazolidinedione based bis-heterocycles 7 (a-r) has been synthesized which exhibited significant PPAR-γ transactivation and blood glucose lowering effect comparable with the standard drugs Pioglitazone and Rosiglitazone. Compounds 7m and 7r did not cause body weight gain and were found to be free from hepatotoxic and cardiotoxic side effects. Compounds 7m and 7r increased PPAR-γ gene expression by 2.10 and 2.00 folds, respectively in comparison to the standard drugs Pioglitazone (1.5 fold) and Rosiglitazone (1.0 fold). Therefore the compounds 7m and 7r may be considered as potential candidates for development of new antidiabetic agents.

Anti-inflammatory and anti-nociceptive activities of Platanus orientalis Linn. and its ulcerogenic risk evaluation.

ETHNOPHARMACOLOGICAL RELEVANCE Leaves of Platanus orientalis Linn. are used in folk medicine as a wound-healer and ophthalmologic agent. Phytol derivatives from the leaves of plane-tree show anti-ulcer activity. Its analgesic and anti-inflammatory effects for knee pain were known to Persian scientists and hakims. MATERIALS AND METHODS The ethanolic extract of Platanus orientalis Linn. and its various fractions were given at a dose of 100mg/kg po and 200mg/kg po for testing their anti-inflammatory activity by carrageenan induced hind paw edema. The analgesic activity of the ethanolic extract and its fractions has been carried out by tail-flick method and writhing test at a dosage of 200mg/kg po. Gastric ulceration studies have been further carried out to study the ulcerogenic risk evaluation of the ethanolic extract and its various fractions at a dose of 600mg/kg body weight. RESULTS Among the tested fractions, chloroform fraction exhibited better inhibition (68.33%) at 200mg/kg po dosage when compared to the standard drug Ibuprofen (66.66%) after 3h in the carrageenan induced hind paw edema. The ethanolic extract and all its fractions especially the chloroform (p<0.01) showed significant analgesic activity with insignificant ulceration as compared to the standard drug i.e. Ibuprofen. The histopathological study of ethanolic extract and its fractions revealed that none of them cause ulcer. CONCLUSION The present study indicates that Platanus orientalis Linn. has significant anti-inflammatory and analgesic effect.

Synthesis of novel 8-hydroxy quinolin based 1,3,4-oxadiazoles and S-substituted 1,2,4-triazole derivatives and evaluation of their anti-inflammatory, analgesic, ulcerogenic and anti-microbial activities.

A series of novel 2-[4-aryl-5-{(quinolin-8-yloxy)methyl}-4H-1,2,4-triazol-3-ylthio]-1-arylethanones (6a-6j) and 8-{(5-aryl-1,3,4-oxadiazol-2-yl)methoxy}quinolines (7a-7d) were synthesized from the corresponding 4-arnyl-1-(2- quinolin-8-yloxy)acetyl) thiosemicarbazides (4a-4d) and hydrazides (3) respectively. The prepared compounds were screened for their anti-inflammatory, analgesic, ulcerogenic and antimicrobial activities. The anti-inflammatory activities were determined by carrageenan induced rat paw edema method. Compounds 6c, 6d, 6f 6j, 7b and 7e significantly inhibited the rat paw edema depending upon the dose employed. These compounds exhibited insignificant ulceration compared to the standard drug Indomethacin. The compounds were also evaluated for their in vitro antimicrobial activity. Some compounds have shown moderate to good activity whereas compound 7b has shown significant zone of inhibition compared to the standard drug Ampicillin against gram negative microorganisms.

Design, Synthesis, and Biological Evaluation of Thiazolidine-2,4-dione Conjugates as PPAR-γ Agonists.

A library of synthesized conjugates of phenoxy acetic acid and thiazolidinedione 5a–m showed potent peroxisome proliferator activated receptor‐γ (PPAR‐γ) transactivation as well as significant blood glucose lowering effect comparable to the standard drugs pioglitazone and rosiglitazone. Most of the compounds showed higher docking scores than the standard drug rosiglitazone in the molecular docking study. Compounds 5l and 5m exhibited PPAR‐γ transactivation of 54.21 and 55.41%, respectively, in comparison to the standard drugs pioglitazone and rosiglitazone, which showed 65.94 and 82.21% activation, respectively. Compounds 5l and 5m significantly lowered the blood glucose level of STZ‐induced diabetic rats. Compounds 5l and 5m lowered the AST, ALT, and ALP levels more than the standard drug pioglitazone. PPAR‐γ gene expression was significantly increased by compound 5m (2.00‐fold) in comparison to the standard drugs pioglitazone (1.5‐fold) and rosiglitazone (1.0‐fold). Compounds 5l and 5m did not cause any damage to the liver and could be considered as promising candidates for the development of new antidiabetic agents.

Synthesis of novel benzimidazole acrylonitriles for inhibition of Plasmodium falciparum growth by dual target inhibition

Antimalarial drug resistance has emerged as a threat for treating malaria, generating a need to design and develop newer, more efficient antimalarial agents. This research aimed to identify novel leads as antimalarials. Dual receptor mechanism could be a good strategy to combat developing drug resistance. A series of benzimidazole acrylonitriles containing 18 compounds were designed, synthesized and evaluated for cytotoxicity, heme binding, ferriprotoporphyrin IX biomineralisation inhibition, and falcipain‐2 enzyme assay. Furthermore, in silico docking and MD simulation studies were also performed.The tests revealed quite encouraging results. Three compounds, viz. R‐01 (0.69 μM), R‐04 (1.60 μM), and R‐08 (1.61 μM), were found to have high antimalarial activity. These compounds were found to be in bearable cytotoxicity limits and their biological assay suggested that they had inhibitory activity against falcipain‐2 and hemozoin formation. The docking revealed the binding mode of benzimidazole acrylonitrile derivatives and MD simulation studies revealed that the protein‐ligand complex was stable. The agents exhibit good hemozoin formation inhibition activity and, hence, may be utilized as leads to design a newer drug class to overcome the drug resistance of hemozoin formation inhibitors such as chloroquine.

In vitro Antimicrobial Efficiency of Crude Extracts of Wild Jatropha glauca Plant Leaves Grown Naturally at Al-Baha Region, KSA

The crude extracts from leaves of Jatropha glauca plant grown naturally at Al-Baha region obtained by extraction with ethanol and fractionated using three solvents: petroleum ether, ethyl acetate and methanol were investigated for their in vitro antimicrobial susceptibility. The antimicrobial activity were evaluated against two bacterial strains S. aureus and E. coli, and two common fungal strains Candida albicans and Candida krusei using disc diffusion assay. The crude ethanolic extract and its fractions methanolic and ethyl acetate showed an inhibitory effect against both bacterial and fungal microorganisms. The petroleum ether fraction had no antimicrobial effect. The ethanolic crude extract and methanolic fraction showed higher zone of inhibition, while the ethyl acetate fraction showed the least activity against both bacterial strains. The methanolic fraction was found to possess lowest MIC ≥250 μgml−1 against both tested bacterial strains. Similarly, the ethanolic crude extract and methanol fraction showed zone of inhibition against tested fungal strains with methanolic fraction showed the highest zone of inhibition. However, these observations indicated that the ethanolic crude extract and its methanolic and ethyl acetate fractions exhibited some antimicrobial potency that proves the leaves contain some gradients that have antibacterial and antifungal potential.