New direct inhibitors of InhA with antimycobacterial activity based on a tetrahydropyran scaffold

Autor:	David Barros, Robert J. Young, Roman Šink, Chun-wa Chung, Matej Živec, Daniel Alvarez-Gomez, Emilio Alvarez-Ruiz, Lourdes Encinas, Esther Pérez-Herrán, María Martínez-Hoyos, Stanislav Gobec, Julia Castro-Pichel, Stane Pajk, Alfonso Mendoza-Losana, Margarete Neu, Izidor Sosič, Máire A. Convery, Lluís Ballell-Pages
Rok vydání:	2016
Předmět:	Models Molecular 0301 basic medicine medicine.drug_class Stereochemistry Antitubercular Agents Microbial Sensitivity Tests Antimycobacterial 01 natural sciences Bacterial protein Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound Bacterial Proteins Drug Discovery medicine Humans Tuberculosis Structure–activity relationship Cytotoxicity Pyrans Pharmacology 010405 organic chemistry Chemistry INHA Organic Chemistry Mycobacterium tuberculosis General Medicine Tetrahydropyran Combinatorial chemistry 0104 chemical sciences 030104 developmental biology Oxidoreductases
Zdroj:	European Journal of Medicinal Chemistry. 112:252-257
ISSN:	0223-5234
Popis:	Tetrahydropyran derivative 1 was discovered in a high-throughput screening campaign to find new inhibitors of mycobacterial InhA. Following initial in-vitro profiling, a structure-activity relationship study was initiated and a focused library of analogs was synthesized and evaluated. This yielded compound 42 with improved antimycobacterial activity and low cytotoxicity. Additionally, the crystal structure of InhA in complex with inhibitor 1 was resolved, to reveal the binding mode and provide hints for further optimization.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d9785662700a98df8dac761fbd4f9570 https://doi.org/10.1016/j.ejmech.2016.02.008 Zobrazit plný text záznamu Full Text from ScienceDirect