Journal article
C4-Phenylthio beta-lactams: Effect of the chirality of the beta-lactam ring on antimicrobial activity
Bioorganic & medicinal chemistry, v 27(20), 115050
15 Oct 2019
PMID: 31474471
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
C4-phenylthio beta-lactams are a new family of antibacterial agents that have activity against two phylogenetically distant bacteria - Mycobacterium tuberculosis (Mtb) and Moraxella catarrhalis (M. cat). These compounds are effective against beta-lactamase producing Mtb and M. cat unlike the clinically relevant beta-lactam antibiotics. The structure-activity relationship for the C4 phenylthio beta-lactams has not yet been completely defined. Earlier efforts in our laboratories established that the C4-phenylthio substituent is essential for antimicrobial activity, while the N1 carbamyl substituent plays a more subtle role. In this present study, we investigated the role that the stereochemistry at C4 plays in these compounds antibacterial activity. This was achieved by synthesizing and testing the antimicrobial activity of diastereomers with a chiral carbamyl group at N1. Our findings indicate that a strict stereochemistry for the C4-phenylthio beta-lactams is not required to obtain optimal anti-Mtb and anti-M. cat activity. Furthermore, the structure-bioactivity profiles more closely relate to the electronic requirement of the phenylthiogroup. In addition, the MICs of Mtb are sensitive to growth medium composition. Select compounds showed activity against non-replicating and multi-drug resistant Mtb.
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Details
- Title
- C4-Phenylthio beta-lactams: Effect of the chirality of the beta-lactam ring on antimicrobial activity
- Creators
- Dina Lloyd - Drexel University, A.J. Drexel Autism InstituteKriti Arora - National Institutes of HealthBalbina J. Plotkin - Midwestern UniversityJacalyn M. Green - Midwestern UniversityHelena I. Boshoff - National Institutes of HealthClifton Barry - National Institutes of HealthJeffrey Deschamps - United States Naval Research LaboratoryMonika I. Konaklieva - American University
- Publication Details
- Bioorganic & medicinal chemistry, v 27(20), 115050
- Publisher
- Elsevier
- Number of pages
- 17
- Grant note
- Intramural Research Program of the NIAID, NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) Midwestern University, Office of Research and Sponsored Programs, Downers Grove, IL American University, Washington, D.C. Mellon Fund
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- A.J. Drexel Autism Institute
- Web of Science ID
- WOS:000486383500005
- Scopus ID
- 2-s2.0-85071403323
- Other Identifier
- 991021860706404721
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InCites Highlights
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Chemistry, Medicinal
- Chemistry, Organic