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Bioorganic & medicinal chemistry
11 01, 2019;27 (21): 115095.

Tryptoline-based benzothiazoles re-sensitize MRSA to ��-lactam antibiotics.

Xinfeng Wang, Jinsen Chen, Wei Wang, Anna Jaunarajs, Xiang Wang
Author Information
  1. Xinfeng Wang: Department of Chemistry, University of Colorado, Boulder, CO 80309, United States.
  2. Jinsen Chen: Department of Chemistry, University of Colorado, Boulder, CO 80309, United States.
  3. Wei Wang: Department of Chemistry, University of Colorado, Boulder, CO 80309, United States.
  4. Anna Jaunarajs: Department of Chemistry, University of Colorado, Boulder, CO 80309, United States.
  5. Xiang Wang: Department of Chemistry, University of Colorado, Boulder, CO 80309, United States. Electronic address: xiang.wang@colorado.edu.
PMID: 31521461 DOI: 10.1016/j.bmc.2019.115095

Abstract

Resistance-modifying agents (RMAs) offer a promising solution to combat bacterial antibiotic resistance. Here we report the discovery and structure-activity relationships of a new class of RMAs with a novel tryptoline-based benzothiazole scaffold. Our most potent compound in this series (4ad) re-sensitizes multiple MRSA strains to cephalosporins at low concentrations (2�����g/mL) and has low mammalian cytotoxicity with a half growth inhibitory concentration (GI)���>���100�����g/mL in human cervical carcinoma (HeLa) cells. In addition, the same core scaffold with different substitutions also gives good antibacterial activity against MRSA.

Keywords

Bacterial antibiotic resistance Methicillin-resistant Staphylococcus aureus (MRSA) Resistance-modifying agents (RMAs) Structure-activity relationship (SAR) Tryptoline-based benzothiazoles ��-lactam antibiotics

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Grants

  1. R21 AI121581/NIAID NIH HHS
  2. R33 AI121581/NIAID NIH HHS

MeSH Term

Anti-Bacterial Agents
Benzothiazoles
Carbolines
Cefazolin
Cefuroxime
Drug Resistance, Bacterial
HeLa Cells
Humans
Methicillin-Resistant Staphylococcus aureus
Microbial Sensitivity Tests
Molecular Structure
Structure-Activity Relationship

Chemicals

Anti-Bacterial Agents
Benzothiazoles
Carbolines
tryptoline
Cefazolin
Cefuroxime
Journal Article Research Support, N.I.H., Extramural
Article has an altmetric score of 4

Word Cloud

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