Identification of a Novel Series of N-Phenyl-5-[(2-phenylbenzimidazol-1-yl)methyl]-1,3,4-oxadiazol-2-amines as Potent Antioxidants and Radical Scavengers

• Published in: Archiv der Pharmazie (Weinheim) Vol. 347; no. 4; pp. 276 - 282
• Main Authors: Ayhan-Kilcigil, Gulgun, Kus, Canan, Coban, Tulay, Ozdamar, Elcin D, Can-Eke, Benay
• Format: Journal Article
• Language: English; German
• Published: WEINHEIM Blackwell Publishing Ltd 01.04.2014; Wiley; Wiley Subscription Services, Inc
• Subjects: Amines - chemical synthesis; Amines - chemistry; Amines - pharmacology; Animals; Antioxidants; Antioxidants - chemical synthesis; Antioxidants - chemistry; Antioxidants - pharmacology; Benzimidazoles; Chemistry; Chemistry, Medicinal; Chemistry, Multidisciplinary; Cytochrome P-450 CYP1A1 - antagonists & inhibitors; Cytochrome P-450 CYP1A1 - metabolism; DPPH; EROD; Free Radical Scavengers - chemistry; Free Radical Scavengers - pharmacology; Free radicals; Free Radicals - metabolism; Life Sciences & Biomedicine; Lipid peroxidation; Lipid Peroxidation - drug effects; Male; Microsomes, Liver - drug effects; Microsomes, Liver - metabolism; Oxadiazoles; Oxadiazoles - chemical synthesis; Oxadiazoles - chemistry; Oxadiazoles - pharmacology; Pharmacology & Pharmacy; Physical Sciences; Rats; Rats, Wistar; Science & Technology; Structure-Activity Relationship; Benzimidazoles; EROD; Oxadiazoles; DPPH; Lipid peroxidation; MECHANISMS; ANTIFUNGAL; LIPID PEROXIDE FORMATION
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/ardp.201300324

In this study, some novel 5‐[[2‐(phenyl/p‐chlorophenyl)‐benzimidazol‐1‐yl]‐methyl]‐N‐substituted phenyl‐1,3,4‐oxadiazol‐2‐amine derivatives (28–45) with an oxadiazole ring were synthesized. The antioxidant properties and radical scavenging activities of the compounds were investigated employing various in vitro systems: hepatic microsomal NADPH‐dependent inhibition of lipid peroxidation levels, scavenging of DPPH free radicals, and inhibition of microsomal ethoxyresorufin O‐deethylase activity (EROD). Compounds 34 and 41 were found to be good scavengers of DPPH radicals (76% and 84%) when compared to BHT (90%). Almost all of the compounds examined were found to possess a good inhibitor effect on the microsomal EROD activity. Moreover, 32 and 41 were more active analogs (97% and 98%) on the microsomal EROD activity than caffeine (85%). The antioxidant properties of some novel benzimidazole derivatives, i.e., 5‐[[2‐(phenyl/p‐chlorophenyl)benzimidazol‐1‐yl]methyl]‐N‐substituted phenyl‐1,3,4‐oxadiazol‐2‐amine derivatives (28–45) having an oxadiazole ring instead of thiadiazole and triazole rings, are described.