Kalim Javed

Synthesis and antiinflammatory activity of some new 1,3,5-trisubstituted pyrazolines bearing benzene sulfonamide

Nineteen new 2-pyrazoline bearing benzenesulfonamide derivatives were synthesized by condensing chalcones with 4-hydrazinonbenzenesulfonamide hydrochloride. Their chemical structures were proved by means of IR, (1)H NMR, (13)C NMR, mass spectroscopic and elemental analyses data. These compounds were tested at dose of 20mg/kg for their anti-inflammatory activity in carrageenan-induced rat paw edema model and volume of paw edema was measured at 0, 3 and 5h. Two compounds 3k and 3l were found to be more active than celecoxib throughout the study (at 3 and 5h). While two other compounds 3m and 3n showed more potent activity than celecoxib at 5h. They are devoid of ulcerogenic potential when administered orally at a dose of 60 mg/kg. Compounds (3k-m) showed COX-1 and COX-2 inhibitory activity at 0.05 microM.

Synthesis and biological evaluation of some new 2-pyrazolines bearing benzene sulfonamide moiety as potential anti-inflammatory and anti-cancer agents.

Eight novel 2-pyrazolines (2a-h) were synthesized by the reaction of appropriate chalcones/flavanones with 4-hydrazinonbenzenesulfonamide hydrochloride and tested for anti-inflammatory and anti-cancer activities. Two compounds 2c and 2e showed good anti-inflammatory activity which is comparable to the reference drug celecoxib in carrageenan-induced rat paw edema bioassay and found safe from the point of view of ulcer induction. Compounds 2c and 2e showed very mild inhibition against the enzymatic activity of ovine COX-1 and COX-2 (in vitro). The compounds 2c and 2f exhibited considerable antitumor activity against tested 60 human tumor cell lines. Specifically, compound 2f exhibited promising anti-proliferative activity with GI(50) values less than 2 μM particularly against MOLT-4 (1.94), SR (1.28) in leukemia cancer, EKVX (1.88) in non small cell lung cancer, COLO 205 (1.69) in colon cancer.

Synthesis of some new 1,3,5-trisubstituted pyrazolines bearing benzene sulfonamide as anticancer and anti-inflammatory agents

Thirteen new 2-pyrazoline derivatives bearing benzenesulfonamide moiety (2a-m) were synthesized by condensing appropriate chalcones with 4-hydrazinonbenzenesulfonamide hydrochloride and tested for anticancer and anti-inflammatory actions. According to the protocol of the National Cancer Institute (NCI) in vitro disease-oriented human cells screening panel assay compounds 2b, 2c, 2e, 2f and 2g exhibited considerable antitumor activities against the entire tested tumor cell lines and showed effective growth inhibition GI(50) (MG-MID) values of 2.63, 2.57, 6.61, 3.31 and 2.57μM, respectively, beside a cyclostatic activity TGI (MG-MID) 9.54, 8.51, 24.0, 19.9 and 8.71μM, respectively. Two compounds 2g and 2k showed more potent anti-inflammatory activity than celecoxib at 5h in carrageenan-induced rat paw edema bioassay. These compounds (2g and 2k) proved to have superior gastrointestinal safety profiles as compared to celecoxib, when tested for their ulcerogenic effects. Compounds 2g and 2k showed no inhibition against the enzymatic activity of bovine COX-2 (in vitro).

Synthesis and evaluation of anticancer activity of some novel 6-aryl-2-(p-sulfamylphenyl)-pyridazin-3(2H)-ones.

A series of novel pyridazinone derivatives bearing benzenesulfonamide moiety (2a-h) has been synthesized by the condensation of appropriate aroylacrylic acid and 4-hydrazinobenzenesulfonamide hydrochloride in ethanol. Five derivatives (2a, 2b, 2d, 2g and 2h) were evaluated for their anticancer activity toward human cancer cell lines by the National Cancer Institute. The 2h showed remarkable activity against SR (leukemia) and NCI-H522 (non-small cell lung) with a GI(50) value of less than 0.1 μM. It also displayed good activity against leukemia (CCRF-CEM, HL-60 (TB), K-562, MOLT-4, RPMI-8226), non-small cell lung cancer (NCI-H460), colon (HCT-116, HCT-15, HT29, KMI2, SW-620), CNS (SF-295), melanoma (MALME-3M, M14, MDA-MB-435 SK-MEL-5), ovarian (OVCAR-3, NCI/ADR-RES) and breast (MCF7) cancer cell lines with a GI(50) less than 1.0 μM. The acute toxicity study of 2h indicated that it is well tolerated intra-peritoneally (400 mg/kg) by athymic nude mice. The 2h may possibly be used as lead compound for developing new anticancer agents.

Protective effect of ginger oil on aspirin and pylorus ligation-induced gastric ulcer model in rats

The present investigation was performed in aspirin and pylorus ligation-induced ulcer model in Wistar rats, in which ability of ginger oil to provide gastric protection was studied at two different doses, 0.5 and 1 g/kg po. Gastric protection was evaluated by measuring the ulcer index, serum γ-GTP levels, total acidity of gastric juice and gastric wall mucus thickness. The results obtained in the present study indicated that ginger oil has a protective action against gastric ulcers induced by aspirin plus pylorus ligation in Wistar rats.

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 and biological evaluation of some novel 6-aryl-2-(p-sulfamylphenyl)-4,5-dihydropyridazin-3(2H)-ones as anti-cancer, antimicrobial, and anti-inflammatory agents

A series of 6-aryl-2-(p-sulfamylphenyl)-4,5-dihydropyridazin-3(2H)-ones (2a–j) were synthesized by condensation of the appropriate β-aroylpropionic acid and 4-hydrazinobenzenesulfonamide hydrochloride in ethanol and tested for anti-cancer, anti-inflammatory, and antimicrobial actions. According to the protocol of the National Cancer Institute (NCI) in vitro disease-oriented human cells screening panel assay, compound 2g showed high activity against HL-60 (TB) (leukemia), SR (leukemia), NCI-H522 (non-small-cell lung cancer), and BT-549 (breast cancer) with a GI50 value of less than 2 μM. Two compounds (2c and 2f) were found to have promising anti-inflammatory activity, while a fair number of compounds showed good antifungal activity.

α-amyrin derivatives from Corchorus depressus

Abstract From the whole plant of Corchorus depressus , in addition to sitosterol glucoside, sitosterol, apigenin and luteolin, three new α-amyrin derivatives, cordepressic acid, cordepressenic acid and cordepressin, have been isolated and their structures established by spectral data and chemical evidence.

Synthesis and evaluation of some new pyrazoline substituted benzenesulfonylureas as potential antiproliferative agents.

Twenty six new pyrazoline substituted benzenesulfonylureas (2a-z) were synthesized and tested for in vitro anticancer activity. Fourteen derivatives (2i, 2k-2p, 2r, 2s-2x) were screened for their antiproliferative activity towards 60 human cancer cell lines by the National Cancer Institute (USA). Among them four compounds (2i, 2n, 2v and 2x) exhibited significant growth inhibition and further screened at 10-fold dilutions of five different concentrations (0.01, 0.1, 1, 10 and 100 μM). The compounds 2i, 2n, 2v and 2x showed effective growth inhibition (GI50 MID) values of 2.62, 3.93, 3.33, 3.74 μM respectively beside cytostatic activity TGI (MG-MID) values of 8.42, 65.80, 24.00 and 36.06 μM respectively. The compound 2i displayed remarkable antiproliferative activity in 8 different cell lines with GI50 less than 2 μM. Compounds 2n, 2v and 2x also displayed good antiproliferative activity against 11, 18 and 14 different cell lines respectively with GI50 less than 3 μM.

Trapa natans L. root extract suppresses hyperglycemic and hepatotoxic effects in STZ-induced diabetic rat model.

ETHNOPHARMACOLOGICAL RELEVANCE Trapa natans L. has a folkloric reputation as nutrient, appetizer and astringent. Its utility as antidiabetic, anticancer, diuretic, aphrodisiac, antidiarrhoeal and in many other maladies is well reported in the literature. Therefore, the present study has been carried out to study the antihyperglycemic effect of root extract of Trapa natans L. and its various fractions. Furthermore, hepatotoxic effects and lipid peroxidation risks have also been evaluated. METHODS The ethanol extract and its successive fractions obtained from roots of Trapa natans have been administered in sucrose loaded and STZ- induced diabetic Wistar rats at doses of 50, 100 and 200mg/kg b.w. Glibenclamide was used as positive control. The evaluation of protective effects of extract as well as fractions against hepatotoxicity and lipid peroxidation at 600mg/kg b.w. has also been carried out. RESULTS The methanol fraction emerged as the most potent antihyperglycemic fraction. It has also been found that the ethanolic extract as well as its fractions did not cause any lipid peroxidation and hepatotoxicity risks. CONCLUSION It can be concluded that the intense investigations of the methanol fraction obtained from Trapa natans root extract can be done to provide an alternative natural therapy for hyperglycemia.