Indole-nitroimidazole conjugates as efficient manipulators to decrease the genes expression of methicillin-resistant Staphylococcus aureus.

Autor: Li ZZ; Key Laboratory of Applied Chemistry of Chongqing Municipality, Institute of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, China., Tangadanchu VKR; Key Laboratory of Applied Chemistry of Chongqing Municipality, Institute of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, China., Battini N; Key Laboratory of Applied Chemistry of Chongqing Municipality, Institute of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, China., Bheemanaboina RRY; Key Laboratory of Applied Chemistry of Chongqing Municipality, Institute of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, China., Zang ZL; Key Laboratory of Applied Chemistry of Chongqing Municipality, Institute of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, China. Electronic address: zhangsl@cqu.edu.cn., Zhang SL; Innovative Drug Research Centre, Chongqing University, Chongqing, 401331, PR China. Electronic address: zhonglinzang@swu.edu.cn., Zhou CH; Key Laboratory of Applied Chemistry of Chongqing Municipality, Institute of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, China. Electronic address: zhouch@swu.edu.cn.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2019 Oct 01; Vol. 179, pp. 723-735. Date of Electronic Publication: 2019 Jul 02.
DOI: 10.1016/j.ejmech.2019.06.093
Abstrakt: The biological resistance of methicillin-resistant staphylococcus aureus (MRSA) has pushed synthetic antibiotics to the forefront. To combat the resistance of MRSA, our new effort directed towards the development of novel structural candidates of enone-bridged indole nitroimidazole scaffolds, and wished to shed some light on the combination of some single pharmacophore with different biological activities. Bioassay revealed that the active compound 4b gave a satisfactory inhibition on MRSA (MIC = 1 μg/mL) and could effectively prevent the development of bacterial resistance. Mechanism exploration indicated that molecule 4b could not only intercalate into MRSA deoxyribonucleic acid (DNA), but also permeate MRSA membrane and bind with penicillin-binding protein 2a (PBP2a), then decreased the expression of three relevant genes in MRSA. Furthermore, it was able to be stored and carried by human serum albumin (HSA), and the participation of metal ions in 4b-HSA system was helpful to improve the supramolecular transport behavior. Hybrid 4b also exhibited low cytotoxicity towards normal lung epithelial cell line BEAS-2B.
(Copyright © 2019 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: