Novel 1,2,4-oxadiazole/pyrrolidine hybrids as DNA gyrase and topoisomerase IV inhibitors with potential antibacterial activity

DNA gyrase is a promising target for antibacterial agents. Several classes of small-molecule inhibitors have been discovered in recent decades, but none of these have reached the market. We have designed a small library of 1,2,4-oxadiazole/pyrrolidine hybrids with mid nanomolar inhibitory and potent...

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Autores principales:	Firas Obaid Arhema Frejat, Yaquan Cao, Hongjin Zhai, Salah A. Abdel-Aziz, Hesham A.M. Gomaa, Bahaa G.M. Youssif, Chunli Wu
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	1,2,4-Oxadiazole Gyrase Topoisomerase Pyrrolidine Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/120d5a647ab344a98570653092417f49
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spelling	oai:doaj.org-article:120d5a647ab344a98570653092417f492021-11-20T04:58:14ZNovel 1,2,4-oxadiazole/pyrrolidine hybrids as DNA gyrase and topoisomerase IV inhibitors with potential antibacterial activity1878-535210.1016/j.arabjc.2021.103538https://doaj.org/article/120d5a647ab344a98570653092417f492022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1878535221005530https://doaj.org/toc/1878-5352DNA gyrase is a promising target for antibacterial agents. Several classes of small-molecule inhibitors have been discovered in recent decades, but none of these have reached the market. We have designed a small library of 1,2,4-oxadiazole/pyrrolidine hybrids with mid nanomolar inhibitory and potent antibacterial activities against DNA gyrase and topoisomerase IV. Compounds 9, 15, 16, 19, and 21 inhibited Escherichia coli DNA gyrase to a similar extent as the reference compound, novobiocin, with inhibitory values ranging from 120 nM to 270 nM. Compound 16 was one of the most potent compounds in the series, with an IC50 value of 120 nM against E. coli gyrase, which is lower than the IC50 value of novobiocin (170 nM). Compound 16 had the highest inhibitory activity, with minimum inhibitory concentrations (MIC) of 24 and 62 ng/mL against Staphylococcus aureus and E. coli, respectively, which compared favorably with ciprofloxacin (30 and 60 ng/mL, respectively). Compounds 9, 15, 19, and 21 were similar to novobiocin in terms of their activity against E. coli and S. aureus topoisomerase IV, while compound 16 was more potent than novobiocin.Firas Obaid Arhema FrejatYaquan CaoHongjin ZhaiSalah A. Abdel-AzizHesham A.M. GomaaBahaa G.M. YoussifChunli WuElsevierarticle1,2,4-OxadiazoleGyraseTopoisomerasePyrrolidineChemistryQD1-999ENArabian Journal of Chemistry, Vol 15, Iss 1, Pp 103538- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	1,2,4-Oxadiazole Gyrase Topoisomerase Pyrrolidine Chemistry QD1-999
spellingShingle	1,2,4-Oxadiazole Gyrase Topoisomerase Pyrrolidine Chemistry QD1-999 Firas Obaid Arhema Frejat Yaquan Cao Hongjin Zhai Salah A. Abdel-Aziz Hesham A.M. Gomaa Bahaa G.M. Youssif Chunli Wu Novel 1,2,4-oxadiazole/pyrrolidine hybrids as DNA gyrase and topoisomerase IV inhibitors with potential antibacterial activity
description	DNA gyrase is a promising target for antibacterial agents. Several classes of small-molecule inhibitors have been discovered in recent decades, but none of these have reached the market. We have designed a small library of 1,2,4-oxadiazole/pyrrolidine hybrids with mid nanomolar inhibitory and potent antibacterial activities against DNA gyrase and topoisomerase IV. Compounds 9, 15, 16, 19, and 21 inhibited Escherichia coli DNA gyrase to a similar extent as the reference compound, novobiocin, with inhibitory values ranging from 120 nM to 270 nM. Compound 16 was one of the most potent compounds in the series, with an IC50 value of 120 nM against E. coli gyrase, which is lower than the IC50 value of novobiocin (170 nM). Compound 16 had the highest inhibitory activity, with minimum inhibitory concentrations (MIC) of 24 and 62 ng/mL against Staphylococcus aureus and E. coli, respectively, which compared favorably with ciprofloxacin (30 and 60 ng/mL, respectively). Compounds 9, 15, 19, and 21 were similar to novobiocin in terms of their activity against E. coli and S. aureus topoisomerase IV, while compound 16 was more potent than novobiocin.
format	article
author	Firas Obaid Arhema Frejat Yaquan Cao Hongjin Zhai Salah A. Abdel-Aziz Hesham A.M. Gomaa Bahaa G.M. Youssif Chunli Wu
author_facet	Firas Obaid Arhema Frejat Yaquan Cao Hongjin Zhai Salah A. Abdel-Aziz Hesham A.M. Gomaa Bahaa G.M. Youssif Chunli Wu
author_sort	Firas Obaid Arhema Frejat
title	Novel 1,2,4-oxadiazole/pyrrolidine hybrids as DNA gyrase and topoisomerase IV inhibitors with potential antibacterial activity
title_short	Novel 1,2,4-oxadiazole/pyrrolidine hybrids as DNA gyrase and topoisomerase IV inhibitors with potential antibacterial activity
title_full	Novel 1,2,4-oxadiazole/pyrrolidine hybrids as DNA gyrase and topoisomerase IV inhibitors with potential antibacterial activity
title_fullStr	Novel 1,2,4-oxadiazole/pyrrolidine hybrids as DNA gyrase and topoisomerase IV inhibitors with potential antibacterial activity
title_full_unstemmed	Novel 1,2,4-oxadiazole/pyrrolidine hybrids as DNA gyrase and topoisomerase IV inhibitors with potential antibacterial activity
title_sort	novel 1,2,4-oxadiazole/pyrrolidine hybrids as dna gyrase and topoisomerase iv inhibitors with potential antibacterial activity
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/120d5a647ab344a98570653092417f49
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Novel 1,2,4-oxadiazole/pyrrolidine hybrids as DNA gyrase and topoisomerase IV inhibitors with potential antibacterial activity

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