A click chemistry approach to pleuromutilin derivatives, evaluation of anti-MRSA activity and elucidation of binding mode by surface plasmon resonance and molecular docking

Novel series of pleuromutilin analogs containing substituted 1,2,3-triazole moieties were designed, synthesised and assessed for their in vitro antibacterial activity against Methicillin-resistant Staphylococcus aureus (MRSA). Initially, the in vitro antibacterial activities of these derivatives aga...

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Autores principales:	Zhe Zhang, Zhao-Sheng Zhang, Xiao Wang, Gao-Lei Xi, Zhen Jin, You-Zhi Tang
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	pleuromutilin 1,2,3-triazole mrsa spr molecular docking Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/46f6b03a12434a56889250592988a7ab
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spelling	oai:doaj.org-article:46f6b03a12434a56889250592988a7ab2021-12-01T14:40:58ZA click chemistry approach to pleuromutilin derivatives, evaluation of anti-MRSA activity and elucidation of binding mode by surface plasmon resonance and molecular docking1475-63661475-637410.1080/14756366.2021.1977931https://doaj.org/article/46f6b03a12434a56889250592988a7ab2021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/14756366.2021.1977931https://doaj.org/toc/1475-6366https://doaj.org/toc/1475-6374Novel series of pleuromutilin analogs containing substituted 1,2,3-triazole moieties were designed, synthesised and assessed for their in vitro antibacterial activity against Methicillin-resistant Staphylococcus aureus (MRSA). Initially, the in vitro antibacterial activities of these derivatives against 4 strains of S. aureus (MRSA ATCC 43300, ATCC 29213, AD3, and 144) were tested by the broth dilution method. Most of the synthesised pleuromutilin analogs displayed potent activities. Among them, compounds 50, 62, and 64 (MIC = 0.5∼1 µg/mL) showed the most effective antibacterial activity and their anti-MRSA activity were further studied by the time-killing kinetics approach. Binding mode investigations by surface plasmon resonance (SPR) with 50S ribosome revealed that the selected compounds all showed obvious affinity for 50S ribosome (KD = 2.32 × 10−8∼5.10 × 10−5 M). Subsequently, the binding of compounds 50 and 64 to the 50S ribosome was further investigated by molecular modelling. Compound 50 had a superior docking mode with 50S ribosome, and the binding free energy of compound 50 was calculated to be −12.0 kcal/mol.Zhe ZhangZhao-Sheng ZhangXiao WangGao-Lei XiZhen JinYou-Zhi TangTaylor & Francis Grouparticlepleuromutilin1,2,3-triazolemrsasprmolecular dockingTherapeutics. PharmacologyRM1-950ENJournal of Enzyme Inhibition and Medicinal Chemistry, Vol 36, Iss 1, Pp 2087-2103 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	pleuromutilin 1,2,3-triazole mrsa spr molecular docking Therapeutics. Pharmacology RM1-950
spellingShingle	pleuromutilin 1,2,3-triazole mrsa spr molecular docking Therapeutics. Pharmacology RM1-950 Zhe Zhang Zhao-Sheng Zhang Xiao Wang Gao-Lei Xi Zhen Jin You-Zhi Tang A click chemistry approach to pleuromutilin derivatives, evaluation of anti-MRSA activity and elucidation of binding mode by surface plasmon resonance and molecular docking
description	Novel series of pleuromutilin analogs containing substituted 1,2,3-triazole moieties were designed, synthesised and assessed for their in vitro antibacterial activity against Methicillin-resistant Staphylococcus aureus (MRSA). Initially, the in vitro antibacterial activities of these derivatives against 4 strains of S. aureus (MRSA ATCC 43300, ATCC 29213, AD3, and 144) were tested by the broth dilution method. Most of the synthesised pleuromutilin analogs displayed potent activities. Among them, compounds 50, 62, and 64 (MIC = 0.5∼1 µg/mL) showed the most effective antibacterial activity and their anti-MRSA activity were further studied by the time-killing kinetics approach. Binding mode investigations by surface plasmon resonance (SPR) with 50S ribosome revealed that the selected compounds all showed obvious affinity for 50S ribosome (KD = 2.32 × 10−8∼5.10 × 10−5 M). Subsequently, the binding of compounds 50 and 64 to the 50S ribosome was further investigated by molecular modelling. Compound 50 had a superior docking mode with 50S ribosome, and the binding free energy of compound 50 was calculated to be −12.0 kcal/mol.
format	article
author	Zhe Zhang Zhao-Sheng Zhang Xiao Wang Gao-Lei Xi Zhen Jin You-Zhi Tang
author_facet	Zhe Zhang Zhao-Sheng Zhang Xiao Wang Gao-Lei Xi Zhen Jin You-Zhi Tang
author_sort	Zhe Zhang
title	A click chemistry approach to pleuromutilin derivatives, evaluation of anti-MRSA activity and elucidation of binding mode by surface plasmon resonance and molecular docking
title_short	A click chemistry approach to pleuromutilin derivatives, evaluation of anti-MRSA activity and elucidation of binding mode by surface plasmon resonance and molecular docking
title_full	A click chemistry approach to pleuromutilin derivatives, evaluation of anti-MRSA activity and elucidation of binding mode by surface plasmon resonance and molecular docking
title_fullStr	A click chemistry approach to pleuromutilin derivatives, evaluation of anti-MRSA activity and elucidation of binding mode by surface plasmon resonance and molecular docking
title_full_unstemmed	A click chemistry approach to pleuromutilin derivatives, evaluation of anti-MRSA activity and elucidation of binding mode by surface plasmon resonance and molecular docking
title_sort	click chemistry approach to pleuromutilin derivatives, evaluation of anti-mrsa activity and elucidation of binding mode by surface plasmon resonance and molecular docking
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/46f6b03a12434a56889250592988a7ab
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A click chemistry approach to pleuromutilin derivatives, evaluation of anti-MRSA activity and elucidation of binding mode by surface plasmon resonance and molecular docking

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