title: 1H-Benzimidazole derivatives as mammalian DNA topoisomerase I inhibitors.
abstract: Benzimidazole is one of the most important heterocyclic groups manifesting various biological properties, such as antibacterial, antifungal, antimicrobial, antiprotozoal and antihelmintic activities. Several benzimidazole derivatives are also active as inhibitors of type I DNA topoisomerases. In this study, three 1H-benzimidazole derivatives with different electronic characteristics at position 5-, namely 5-chloro-4-(1H-benzimidazole-2-yl)phenol (Cpd I), 5-methyl-4-(1H-benzimidazole-2-yl)phenol (Cpd II) and 4-(1H-benzimidazole-2-yl)phenol (Cpd III), were synthesized and evaluated for their effects on mammalian type I DNA topoisomerase activity using quantitative in vitro plasmid supercoil relaxation assays. For the structure elucidation of the compounds, melting points, UV, IR, 1H NMR, 13C NMR, mass spectral data and elemental analyses were interpreted. Among the compounds, 5-methyl-4-(1H-benzimidazole-2-yl)phenol (Cpd II) manifested relatively potent topoisomerase I inhibition.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ege University, Izmir, Turkey.
authors.forename: A Selcen
authors.initials: AS
authors.lastname: Alpan
authors.forename: H Semih
authors.initials: HS
authors.lastname: Gunes
authors.forename: Zeki
authors.initials: Z
authors.lastname: Topcu
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000737:chemistry* / Q000494:pharmacology*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors