title: Nitroimidazolyl hydrazones are better amoebicides than their cyclized 1,3,4-oxadiazoline analogues: In vitro studies and Lipophilic efficiency analysis.
abstract: Two series of compounds with hydrazone derivatives (HZ1-HZl2, 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-HZl2) 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 μM) and HZ9 (IC50 = 0.81 μM) 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.
authors: Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia (Central University), New Delhi-110025, India.
authors: Mohmmad Younus
authors: MY
authors: Wani
authors: Abdul R
authors: AR
authors: Bhat
authors: Amir
authors: A
authors: Azam
authors: Fareeda
authors: F
authors: Athar
mesh_terms: D000563:Amebicides / Q000737:chemistry / Q000494:pharmacology*; D000977:Antiparasitic Agents / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004748:Entamoeba histolytica / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D006835:Hydrazones / Q000737:chemistry / Q000494:pharmacology*; D057927:Hydrophobic and Hydrophilic Interactions; D015394:Molecular Structure; D009593:Nitroimidazoles / Q000737:chemistry / Q000494:pharmacology*; D010069:Oxadiazoles / Q000737:chemistry / Q000494:pharmacology*; D021261:Parasitic Sensitivity Tests; D013329:Structure-Activity Relationship
chemical_list: D000563:Amebicides; D000977:Antiparasitic Agents; D006835:Hydrazones; D009593:Nitroimidazoles; D010069:Oxadiazoles