title: Synthesis and biological activity evaluation of 1H-benzimidazoles via mammalian DNA topoisomerase I and cytostaticity assays.
abstract: Benzimidazoles are important compounds because of their antibacterial, antifungal, antimicrobial, antiprotozoal and antihelmintic activities. Some benzimidazole derivatives also interfere with the reactions of DNA topoisomerases, enzymes functioning at almost all stages of the cell cycle. In this study, nine 1H-benzimidazole derivatives with substituents at positions 2 and 5 were synthesized and the structure of the compounds was elucidated by instrumental methods. The characterized compounds were screened to identify if they interfered with mammalian type I DNA topoisomerase activity via in vitro supercoil relaxation assays. Selected compounds were subjected to cytostatic assays using HeLa (cervix adenocarcinoma), MCF7 (breast adenocarcinoma) and A431 (skin epidermoid carcinoma) cells. Our results showed that 5-chloro-2-(2-hydroxyphenyl)-1H-benzimidazole exerted the most profound topoisomerase I inhibition and cytotoxicity.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ege University, Izmir 35100, Turkey.
authors.forename: Gunes
authors.initials: G
authors.lastname: Coban
authors.forename: Sevil
authors.initials: S
authors.lastname: Zencir
authors.forename: István
authors.initials: I
authors.lastname: Zupkó
authors.forename: Borbála
authors.initials: B
authors.lastname: Réthy
authors.forename: H Semih
authors.initials: HS
authors.lastname: Gunes
authors.forename: Zeki
authors.initials: Z
authors.lastname: Topcu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D054697:Cytostatic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors
chemical_list: D000970:Antineoplastic Agents; D001562:Benzimidazoles; D054697:Cytostatic Agents; D059004:Topoisomerase I Inhibitors