Development of 6-Methanesulfonyl-8-nitrobenzothiazinone Based Antitubercular Agents.


Journal

ACS medicinal chemistry letters
ISSN: 1948-5875
Titre abrégé: ACS Med Chem Lett
Pays: United States
ID NLM: 101521073

Informations de publication

Date de publication:
14 Apr 2022
Historique:
received: 19 11 2021
accepted: 04 03 2022
entrez: 22 4 2022
pubmed: 23 4 2022
medline: 23 4 2022
Statut: epublish

Résumé

The 6-trifluoro substituted 8-nitrobenzothiazinones (BTZs) represent a novel type of antitubercular agents, and their high antimycobacterial activity is related to the inhibition of decaprenylphosphoryl-β-d-ribose 2'-oxidase (DprE1), an enzyme essential for the biosynthesis of mycobacterial cell wall. While extraordinary whole-cell activity was reported for the clinically advanced compound PBTZ169, its poor aqueous solubility signals the potential low bioavailability. To ameliorate the BTZ physiochemical property, a series of 6-methanesulfonyl substituted compounds were designed and prepared, and their antitubercular activity and DprE1 inhibition ability were evaluated. Among these compounds, MsPBTZ169 and compounds

Identifiants

pubmed: 35450361
doi: 10.1021/acsmedchemlett.1c00652
pmc: PMC9014434
doi:

Types de publication

Journal Article

Langues

eng

Pagination

593-598

Informations de copyright

© 2022 American Chemical Society.

Déclaration de conflit d'intérêts

The authors declare no competing financial interest.

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Auteurs

Rui Shi (R)

College of Pharmaceutical Sciences, Soochow University, 199 Renai Road, Suzhou 215123, P. R. China.

Bin Wang (B)

Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Department of Pharmacology, Beijing Tuberculosis and Thoracic Tumor Research, Beijing Chest Hospital, 97 Ma Chang Street, Beijing 101149, P. R. China.

Giovanni Stelitano (G)

Department of Biology and Biotechnology, University of Pavia, Via Ferrata 9, 27100 Pavia, Italy.

Xiaomei Wu (X)

College of Pharmaceutical Sciences, Soochow University, 199 Renai Road, Suzhou 215123, P. R. China.

Yuanyuan Shan (Y)

College of Pharmaceutical Sciences, Soochow University, 199 Renai Road, Suzhou 215123, P. R. China.

Yue Wu (Y)

College of Pharmaceutical Sciences, Soochow University, 199 Renai Road, Suzhou 215123, P. R. China.

Xin Wang (X)

College of Pharmaceutical Sciences, Soochow University, 199 Renai Road, Suzhou 215123, P. R. China.

Laurent R Chiarelli (LR)

Department of Biology and Biotechnology, University of Pavia, Via Ferrata 9, 27100 Pavia, Italy.

Yu Lu (Y)

Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Department of Pharmacology, Beijing Tuberculosis and Thoracic Tumor Research, Beijing Chest Hospital, 97 Ma Chang Street, Beijing 101149, P. R. China.

Chunhua Qiao (C)

College of Pharmaceutical Sciences, Soochow University, 199 Renai Road, Suzhou 215123, P. R. China.

Classifications MeSH