Selective Inhibition of Escherichia coli RNA and DNA Topoisomerase I by Hoechst 33258 Derived Mono- and Bisbenzimidazoles

Autor:	Dev P. Arya, Fenfei Leng, Weidong Wang, Nihar Ranjan, Yuk-Ching Tse-Dinh, Geraldine Fulcrand, Sandra Story, Souvik Sur, Ada King, Muzammil Ahmad
Rok vydání:	2017
Předmět:	Male Methicillin-Resistant Staphylococcus aureus 0301 basic medicine Drug Evaluation Preclinical Chemistry Techniques Synthetic Microbial Sensitivity Tests medicine.disease_cause 01 natural sciences Inhibitory Concentration 50 03 medical and health sciences Cell Line Tumor Drug Discovery Escherichia coli medicine Side chain Humans Isomerases Cytotoxicity biology 010405 organic chemistry Chemistry Escherichia coli Proteins Topoisomerase RNA DNA Molecular biology Anti-Bacterial Agents 0104 chemical sciences Molecular Docking Simulation 030104 developmental biology Duplex (building) Cell culture Bisbenzimidazole biology.protein Molecular Medicine Benzimidazoles Drug Screening Assays Antitumor Topoisomerase I Inhibitors Antibacterial activity
Zdroj:	Journal of Medicinal Chemistry. 60:4904-4922
ISSN:	1520-4804 0022-2623
DOI:	10.1021/acs.jmedchem.7b00191
Popis:	A series of Hoechst 33258 based mono- and bisbenzimidazoles have been synthesized and their Escherichia coli DNA topoisomerase I inhibition, binding to B-DNA duplex, and antibacterial activity has been evaluated. Bisbenzimidazoles with alkynyl side chains display excellent E. coli DNA topoisomerase I inhibition properties with IC50 values 32 μg/mL). Bisbenzimidazoles showed varied stabilization of B-DNA duplex (1.2−23.4 °C), and cytotoxicity studies show similar variation dependent upon the side chain length. ...
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1c7df45b7862bf1ed96fad95a2d11871 https://doi.org/10.1021/acs.jmedchem.7b00191 Zobrazit plný text záznamu