Identification of benzothiazones containing a hexahydropyrrolo[3,4-c]pyrrol moiety as antitubercular agents against MDR-MTB

IMB1603, a spiro-benzothiazone compound discovered by our lab, displayed potent anti-MTB activity in vitro and in vivo. In this study, we reported a series of new BTZs containing the hexahydropyrrolo[3,4-c]pyrrol moiety based on the structure of IMB1603. Among them, BTZs 11 and 24 displayed potent a...

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Detalles Bibliográficos
Autores principales: Ma, Xican, Han, Bing, Wang, Aoyu, Yang, Lu, Huang, Menghao, Chowdhury, Kushan, Gu, Jian, Zhang, Kai, Lv, Kai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2020
Materias:
Chemistry
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9051945/
https://www.ncbi.nlm.nih.gov/pubmed/35498504
http://dx.doi.org/10.1039/d0ra00750a
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author Ma, Xican
Han, Bing
Wang, Aoyu
Yang, Lu
Huang, Menghao
Chowdhury, Kushan
Gu, Jian
Zhang, Kai
Lv, Kai
author_facet Ma, Xican
Han, Bing
Wang, Aoyu
Yang, Lu
Huang, Menghao
Chowdhury, Kushan
Gu, Jian
Zhang, Kai
Lv, Kai
author_sort Ma, Xican
collection PubMed
description IMB1603, a spiro-benzothiazone compound discovered by our lab, displayed potent anti-MTB activity in vitro and in vivo. In this study, we reported a series of new BTZs containing the hexahydropyrrolo[3,4-c]pyrrol moiety based on the structure of IMB1603. Among them, BTZs 11 and 24 displayed potent anti-MTB (MIC < 0.035 μM) and MDR-MTB (MIC, 0.053–0.102 μM) activity, good solubility (1.82–1.85 μg mL(−1)), and low cytotoxicity (CC(50) > 200 μM), suggesting BTZs 11 and 24 may serve as promising candidates for further study. The molecular docking study of 11 toward DprE was also investigated, and revealed that 11 mimicked the binding pattern of PBTZ169 in the active site of DprE1.
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spelling pubmed-90519452022-04-29 Identification of benzothiazones containing a hexahydropyrrolo[3,4-c]pyrrol moiety as antitubercular agents against MDR-MTB Ma, Xican Han, Bing Wang, Aoyu Yang, Lu Huang, Menghao Chowdhury, Kushan Gu, Jian Zhang, Kai Lv, Kai RSC Adv Chemistry IMB1603, a spiro-benzothiazone compound discovered by our lab, displayed potent anti-MTB activity in vitro and in vivo. In this study, we reported a series of new BTZs containing the hexahydropyrrolo[3,4-c]pyrrol moiety based on the structure of IMB1603. Among them, BTZs 11 and 24 displayed potent anti-MTB (MIC < 0.035 μM) and MDR-MTB (MIC, 0.053–0.102 μM) activity, good solubility (1.82–1.85 μg mL(−1)), and low cytotoxicity (CC(50) > 200 μM), suggesting BTZs 11 and 24 may serve as promising candidates for further study. The molecular docking study of 11 toward DprE was also investigated, and revealed that 11 mimicked the binding pattern of PBTZ169 in the active site of DprE1. The Royal Society of Chemistry 2020-04-07 /pmc/articles/PMC9051945/ /pubmed/35498504 http://dx.doi.org/10.1039/d0ra00750a Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Ma, Xican
Han, Bing
Wang, Aoyu
Yang, Lu
Huang, Menghao
Chowdhury, Kushan
Gu, Jian
Zhang, Kai
Lv, Kai
Identification of benzothiazones containing a hexahydropyrrolo[3,4-c]pyrrol moiety as antitubercular agents against MDR-MTB
title Identification of benzothiazones containing a hexahydropyrrolo[3,4-c]pyrrol moiety as antitubercular agents against MDR-MTB
title_full Identification of benzothiazones containing a hexahydropyrrolo[3,4-c]pyrrol moiety as antitubercular agents against MDR-MTB
title_fullStr Identification of benzothiazones containing a hexahydropyrrolo[3,4-c]pyrrol moiety as antitubercular agents against MDR-MTB
title_full_unstemmed Identification of benzothiazones containing a hexahydropyrrolo[3,4-c]pyrrol moiety as antitubercular agents against MDR-MTB
title_short Identification of benzothiazones containing a hexahydropyrrolo[3,4-c]pyrrol moiety as antitubercular agents against MDR-MTB
title_sort identification of benzothiazones containing a hexahydropyrrolo[3,4-c]pyrrol moiety as antitubercular agents against mdr-mtb
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9051945/
https://www.ncbi.nlm.nih.gov/pubmed/35498504
http://dx.doi.org/10.1039/d0ra00750a
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