Saqlain Haider

Synthesis and evaluation of pyrazolines bearing benzothiazole as anti-inflammatory agents

The present study aims at the synthesis of pyrazolines bearing benzothiazole and their evaluation as anti-inflammatory agents. The synthesized compounds were evaluated for their anti-inflammatory potential using carrageenan induced paw edema model. Two compounds 5a and 5d alleviated inflammation more than the standard drug celecoxib. Eight compounds 5 b, 5 c, 5 e, 5 g, 5 h, 6 b, 6 e and 6 f showed anti-inflammatory activity comparable to celecoxib. To understand the mode of action, COX-2 enzyme assay and TNF-α assay were carried out. All the active compounds were assessed for their cytotoxicity. The ulcerogenic risk evaluation was performed on the active compounds that were not found to be cytotoxic. Out of ten active compounds, two compounds (5 d and 6 f) were finally found to be the most potent anti-inflammatory agents attributing to the suppression of the COX-2 enzyme activity and TNF-α production without being either cytotoxic or ulcerogenic.

Synthesis of novel 1,2,3-triazole based benzoxazolinones: their TNF-α based molecular docking with in-vivo anti-inflammatory, antinociceptive activities and ulcerogenic risk evaluation.

A library of novel bis-heterocycles containing benzoxazolinone based 1,2,3-triazoles has been synthesized using click chemistry approach. The compound 3f exhibited potent selective COX-2 inhibition of 59.48% in comparison to standard drug celecoxib (66.36% inhibition). The compound 3i showed significant (p < 0.001, 50.95%), TNF-α inhibitory activity as compared to indomethacin (p < 0.001, 64.01%). The results of the carrageenan induced hind paw oedema showed that compounds 3a, 3f, 3i, 3o, and 3e exhibited potent anti-inflammatory activity in comparison to Indomethacin. The molecular docking studies revealed that 3i exhibits strong inhibitory effect due to the extra stability of the complex because of an extra π-π bond. The histopathology report showed that none of the compounds caused gastric ulceration.

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.

Novel benzenesulfonylureas containing thiophenylpyrazoline moiety as potential antidiabetic and anticancer agents

In the present study a library of twenty six benzenesulfonylureas containing thiophenylpyrazoline moiety has been synthesized. All the compounds were docked against PPAR-γ target. Most of the compounds displayed higher dock score than standard drugs, glibenclamide and rosiglitazone. All the synthesized compounds were primarily evaluated for their antidiabetic effect by oral glucose tolerance test. Further assessment of antidiabetic potential of sixteen active compounds was then done on STZ induced diabetic model. The results of in vivo activity by both the methods were found to be consistent with each other as well as with docking studies. Change in body weight of STZ induced animals post treatment was also assessed at the end of study. In vitro PPAR-γ transactivation assay was performed on active compounds in order to validate docking results and the most active compound 3 k was also shown to elevate gene expression of PPAR-γ. Furthermore, the compounds were screened by National Cancer Institute, Bethesda for anticancer effect and two compounds 3h and 3 i were selected at one dose level since they exhibited sensitivity towards tumor cell lines (mainly melanoma).

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.

Anti-inflammatory and anti-nociceptive activities of two new triterpenoids from Adiantum capillus-veneris Linn.

Two new triterpenoids characterised as 30-normethyl fernen-22-one (capillirone, 1) and hopan-3β-ol (capillirol B, 2), along with two known triterpenoids, 4-α-hydroxyfilican-3-one and 3-β,4-α-dihydroxyfilicane, have been isolated from the ethanolic extract of the fronds of Adiantum capillus-veneris Linn. (Adiantaceae). Compounds 1 and 3 showed significant anti-inflammatory activity with 33.07% (p < 0.01) and 42.30% (p < 0.001) inhibition as compared to indomethacin that exhibited 60.00% (p < 0.001) inhibition after 3 h in the carrageenan-induced hind paw oedema method. Compound 3 showed potent anti-nociceptive activity with 42.37% inhibition as compared to indomethacin that showed 45.34% inhibition in the writhing test.

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.