Synthesis and biological activity evaluation of 1H-benzimidazoles via mammalian DNA topoisomerase I and cytostaticity assays

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 st...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2009-05, Vol.44 (5), p.2280-2285
Main Authors: COBAN, Gunes, ZENCIR, Sevil, ZUPKO, Istvan, RETHY, Borbala, GUNES, H. Semih, TOPCU, Zeki
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - pharmacology
Benzimidazoles - chemical synthesis
Benzimidazoles - pharmacology
Biological and medical sciences
Cell Line, Tumor
Cytostatic Agents - chemical synthesis
Cytostatic Agents - pharmacology
General aspects
Humans
Medical sciences
Pharmacology. Drug treatments
Structure-Activity Relationship
Topoisomerase I Inhibitors
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Summary: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.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2008.06.018