TY - JOUR
T1 - Discovery and Optimization of 6-(1-Substituted pyrrole-2-yl)- s-triazine Containing Compounds as Antibacterial Agents
AU - Green, Keith D.
AU - Pang, Allan H.
AU - Thamban Chandrika, Nishad
AU - Garzan, Atefeh
AU - Baughn, Anthony D.
AU - Tsodikov, Oleg V.
AU - Garneau-Tsodikova, Sylvie
N1 - Publisher Copyright:
© 2022 American Chemical Society. All rights reserved.
PY - 2022/4/8
Y1 - 2022/4/8
N2 - Antimicrobial drug resistance is a major health issue plaguing healthcare worldwide and leading to hundreds of thousands of deaths globally each year. Tackling this problem requires discovery and development of new antibacterial agents. In this study, we discovered novel 6-(1-substituted pyrrole-2-yl)-s-triazine containing compounds that potently inhibited the growth of Staphylococcus aureus regardless of its methicillin-resistant status, displaying minimum inhibitory concentration (MIC) values as low as 1 μM. The presence of a single imidazole substituent was critical to the antibacterial activity of these compounds. Some of the compounds also inhibited several nontubercular mycobacteria. We have shown that these molecules are potent bacteriostatic agents and that they are nontoxic to mammalian cells at relevant concentrations. Further development of these compounds as novel antimicrobial agents will be aimed at expanding our armamentarium of antibiotics.
AB - Antimicrobial drug resistance is a major health issue plaguing healthcare worldwide and leading to hundreds of thousands of deaths globally each year. Tackling this problem requires discovery and development of new antibacterial agents. In this study, we discovered novel 6-(1-substituted pyrrole-2-yl)-s-triazine containing compounds that potently inhibited the growth of Staphylococcus aureus regardless of its methicillin-resistant status, displaying minimum inhibitory concentration (MIC) values as low as 1 μM. The presence of a single imidazole substituent was critical to the antibacterial activity of these compounds. Some of the compounds also inhibited several nontubercular mycobacteria. We have shown that these molecules are potent bacteriostatic agents and that they are nontoxic to mammalian cells at relevant concentrations. Further development of these compounds as novel antimicrobial agents will be aimed at expanding our armamentarium of antibiotics.
KW - MRSA
KW - antibiotic
KW - biofilm
KW - drug discovery
KW - structure-activity relationship
UR - http://www.scopus.com/inward/record.url?scp=85126769758&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85126769758&partnerID=8YFLogxK
U2 - 10.1021/acsinfecdis.1c00450
DO - 10.1021/acsinfecdis.1c00450
M3 - Article
C2 - 35239306
AN - SCOPUS:85126769758
VL - 8
SP - 757
EP - 767
JO - ACS Infectious Diseases
JF - ACS Infectious Diseases
IS - 4
ER -
