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Three new series of 5-aminosalicylic acid derivatives; series I ( 14 , 16 – 18 ), series II ( 19 – 30 ) and series III ( 31 – 41 ) were synthesized as potential dual COX-2/5-LOX inhibitors. Their chemical structures were confirmed using spectroscopic tools including IR, 1 H NMR, 13 C NMR, mass spectroscopy and elemental analyses. The anti-inflammatory activity for all target compounds was evaluated in vivo using carrageenan-induced paw edema. Compound 36 showed the highest anti-inflammatory activity (114.12%) relative to reference drug indomethacin at 4 h interval. Selected derivatives were evaluated in vitro to inhibit ovine COX-1, human recombinant COX-2 and 5-LOX enzymes. Compounds 34 & 35 exhibited significant COX-2 inhibition (IC 50 = 0.10 µM) with significant COX-2 selectivity indices (SI = 135 & 145 respectively) approximate to celecoxib (IC 50 = 0.049 µM, SI = 308.16) and exceeding indomethacin (IC 50 = 0.51 µM, SI = 0.08). Interestingly, all compounds showed superior 5-LOX inhibitory activity about 2–5 times relative to zileuton . Compound 16 was the superlative 5-LOX inhibitor that revealed (IC 50 = 3.41 µM) relative to zileuton (IC 50 = 15.6 µM). Compounds 34 , 35 , 36 and 41 showed significant dual COX-2/5-LOX inhibitions. The gastric ulcerogenic effect of compound 36 was examined on gastric mucosa of albino rats and they showed superior GI safety profile compared with indomethacin . Molecular docking studies of the compounds into the binding sites of COX-1, COX-2 and 5-LOX allowed us to shed light on the binding mode of these novels dual COX and 5-LOX inhibitors.

Herein, we designed and synthesized certain anilinoquinazoline derivatives bearing bulky arylpyridinyl, arylpropenoyl and arylpyrazolyl moieties at the 4' position of the anilinoquinazoline, as potential dual HER2/EGFR kinase inhibitors. A detailed molecular modeling study was performed by docking the synthesized compounds in the active site of the epidermal growth factor receptor (EGFR). The synthesized compounds were further tested for their inhibitory activity on EGFR and HER2 tyrosine kinases. The aryl 2-imino-1,2-dihydropyridine derivatives 5d and 5e displayed the most potent inhibitory activity on EGFR with IC50 equal to 2.09 and 1.94 μM, respectively, and with IC50 equal to 3.98 and 1.04 μM on HER2, respectively. Furthermore, the anti-proliferative activity of these most active compounds on MDA-MB-231 breast cancer cell lines, known to overexpress EGFR, showed an IC50 range of 2.4 and 2.5 μM, respectively.

Oxidative stress associated with insulin -dependent diabetes mellitus is a risk for vascular disorders and diabetic nephropathy. Bitter melon(BME) is a widely used as antioxidant and vasorelaxant. This study to evaluate hypoglycemic, hypolipedimic and antioxidant effects of aqueous Momordica charantia extract against streptozotocin (STZ) induced dia- betes in male rats and explore possible effect of BME on insulin and nitric oxide release. Method: This study was carried on 30 male Sprague-Dawley rats weighing 80-90 g, 60 days old, classified into 3 groups, control, diabetic and treated diabetic group. STZ was given in a dose of 30 mg/kg for 2 consecutive days intraperitoneally (IP). Result: STZ produced a significant increase in serum glucose , triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), urea and creatinine (Cr), significant increase in renal reduced glutathione (GSH), nitric oxide (NO), significant decrease in insulin levels, myeloperoxidase (MPO) and erythrocyte glutathione-S-transferase (EGST)) activities. Oral BME (400 mg/kg/d/8 weeks) significantly ameliorated these effects. Conclusion: Treatment with BME improved DM and its related late conse- quences. Furthermore, it has antioxidant and vasodilator effects. Commonly, BME is a way to surmount the diabetic state and it has vasodilator effects. It may be a promising adjuvant to anti diabetic therapy.

In the present study, a series of 2-aroylindole derivatives were synthesized by phase transfer catalysis (PTC) and were characterized by IR, 1 H-NMR, Mass spectral and Elemental analysis. Indole derivatives 6a-g, 7a-f, 8a-f and 9a-13a were tested for analgesic activity using hot-plate test. Compounds 7b and 8b were tested for antipyretic and anti-inflammatory activity using yeast induced hyperthermia and paw edema in rats. Analgesic activity was shown when indole nucleus was substituted at position 2 and 3 by phenyl and (p-halo)benzoyl moieties respectively, where highest activity was recognised in co mpounds 7b and 8b. Both compounds also exhibited faster, more effective and prolonged reduction in hyperthermia and edema induced in rats compared with indomethacin. Compounds7b and 8b were also tested for ulcerogenic activity in mice, where a lower ulcer ogenic effect was observed compared with indomethacin at all tested dose levels.