Nitroimidazolyl hydrazones are better amoebicides than their cyclized 1,3,4-oxadiazoline analogues: In vitro studies and Lipophilic efficiency analysis

作者：Wani Mohmmad Younus; Bhat Abdul R; Azam Amir; Athar Fareeda^*

来源：European Journal of Medicinal Chemistry, 2013, 64: 190-199.

DOI：10.1016/j.ejmech.2013.03.034

• Acylhydrazone
• Oxadiazoline
• Lipophilic efficiency
• Entamoeba histolytica
• HepG2

Two series of compounds with hydrazone derivatives (HZ1-HZ12, series 1) and oxadiazoline derivatives (OZ1-OZ12, series 2) of the 2-methyl-5-nitro-1H-imidazole scaffold were designed and synthesized. Physicochemical properties and Lipophilic efficiency (LipE) analysis predicted higher intrinsic quality of the acylhydrazone derivatives (series 1) than their corresponding oxadiazoline analogues (series 2). In vitro antiamoebic results supported the above findings and validated that the acylhydrazone derivatives (HZ1-HZI2) show better activity than the oxadiazoline derivatives (OZ1-OZ12). MTT assay, using HepG2 cell line, revealed noncytotoxic nature of the compounds. The most promising results were observed for compounds HZ5 (IC50 = 0.96 mu M) and HZ9 (IC50 = 0.81 mu M) both in silico and in vitro. Analysis of the Lipophilic efficiency (LipE) of the compounds provided new insight for the design of potent and selective amoebicides.

• 出版日期2013-6