Structure-activity relationship analyses of fusidic acid derivatives highlight crucial role of the C-21 carboxylic acid moiety to its anti-mycobacterial activity.


Journal

Bioorganic & medicinal chemistry
ISSN: 1464-3391
Titre abrégé: Bioorg Med Chem
Pays: England
ID NLM: 9413298

Informations de publication

Date de publication:
01 07 2020
Historique:
received: 12 03 2020
accepted: 22 04 2020
pubmed: 5 5 2020
medline: 24 3 2021
entrez: 5 5 2020
Statut: ppublish

Résumé

Fusidic acid (FA) is a potent congener of the fusidane triterpenoid class of antibiotics. Structure-activity relationship (SAR) studies suggest the chemical structure of FA is optimal for its antibacterial activity. SAR studies from our group within the context of a drug repositioning approach in tuberculosis (TB) suggest that, as with its antibacterial activity, the C-21 carboxylic acid group is indispensable for its anti-mycobacterial activity. Further studies have led to the identification of 16-deacetoxy-16β-ethoxyfusidic acid (58), an analog which exhibited comparable activity to FA with an in vitro MIC

Identifiants

pubmed: 32362386
pii: S0968-0896(20)30356-4
doi: 10.1016/j.bmc.2020.115530
pii:
doi:

Substances chimiques

Anti-Bacterial Agents 0
Fusidic Acid 59XE10C19C

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

115530

Informations de copyright

Copyright © 2020 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declared that there is no conflict of interest.

Auteurs

Kawaljit Singh (K)

Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa; Drug Discovery and Development Centre (H3D), University of Cape Town, Rondebosch 7701, South Africa; South African Medical Research Council Drug Discovery and Development Research Unit, University of Cape Town, Rondebosch 7701, South Africa.

Gurminder Kaur (G)

Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa; Drug Discovery and Development Centre (H3D), University of Cape Town, Rondebosch 7701, South Africa.

Petrus Siningu Shanika (PS)

Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa.

Godwin Akpeko Dziwornu (GA)

Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa.

John Okombo (J)

Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa.

Kelly Chibale (K)

Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa; Drug Discovery and Development Centre (H3D), University of Cape Town, Rondebosch 7701, South Africa; South African Medical Research Council Drug Discovery and Development Research Unit, University of Cape Town, Rondebosch 7701, South Africa; Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Rondebosch 7701, South Africa. Electronic address: kelly.chibale@uct.ac.za.

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Classifications MeSH