"Rational Design, Synthesis and Biological Evaluation of Certain Five Membered Ring Heterocycles"

Abstract

The resistant of Acinetobacter baumannii to almost all the available anti-microbial agents and their susceptibility for the epidemic spread, made an urgent need for discovering new targets for inhibition of virulent Acinetobacter baumannii, without stimulation of other resistant. Long chain fatty acid (LCFA) pathway of A. baumannii is a vital factor for bacterial physiology, make it an attractive target for drug discovery. Ole1p (Δ9-fatty acid desaturase enzyme) is a key element in LCFA pathway. It responsible for converting saturated fatty acyl-CoA substrates to monounsaturated fatty acids which is critical for membrane permeability, biofilm formation and surface motility. In this study, the main aim is to design novel thiazol-2(3H)-imine derivatives targeting Ole1p. The design focused on exploration of the previously exposed SAR studies and bioisosteric modifications of the lead compounds. The structure and purity of each final synthesized compound were confirmed by X-ray crystallography, 1H-NMR, 13C- NMR, EI-MS, and elemental analysis.