Abstract

SYNTHESIS, ANTI-INFLAMMATORY AND ANTIMICROBIAL EVALUATION OF NICOTINAMIDES BEARING THIAZOLE AND PYRAZOLINE PHARMACOPHORES.

Zakaria K. Abdel-Samii, Hanan A. Abdel- Fattah*, Amany M. Al-Mahmoudy and Elsayed M. Mahmoud

Abstract

Searching novel, safe and effective anti-inflammatory and antimicrobial agents has remained an evolving research enquiry in the mainstream of inflammatory disorders and microbial infections. In the present investigation series of pyrazoles bearing thiazole and pyridyl moiety as a possible pharmacophore and nicotinamides bearing thiazole moiety were synthesized and assessed for their in vitro antiinflammatory and antimicrobial activity. The structure of newly synthesized compounds were characterized by IR, 1H NMR, 13CNMR, and mass spectral analysis. Cyclooxygenase I and II (COX-I and COXII) inhibition assays were carried out using Celecoxib ,Diclofenac and Indomethacin as standards.The results obtained clearly focus the significance of compounds 2a,2b,2e,2j,2k,2l and 6 as selective COX-II inhibitors. However,their efficacies were associated with lower gastric ulcerogenicity compared to Indomethacin. Compounds 4a,4b,4c,5a, 5b,5c and 5d showed high antimicrobial activity against Gram positive bacteria (Staphylococcus aureus and Micrococcus luteus), moderate activity against Gram negative bacteria (Salmonella typhimurium and Escherchia coli) and high antifungal activity against Candida albicans.

Keywords: Anti-inflammatory, antimicrobial, pyrazoline, pyridine, thiazole, nicotinamide, COX-I, COX-II, ulcerogenicity.