Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, Kentucky 40536-0596, United States.
Department of Microbiology and Immunology, University of Minnesota, 689 23rd Ave SE, Minneapolis, Minnesota 55455-1507, United States.
ACS Infect Dis. 2022 Apr 8;8(4):757-767. doi: 10.1021/acsinfecdis.1c00450. Epub 2022 Mar 3.
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)--triazine containing compounds that potently inhibited the growth of 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.
抗菌药物耐药性是一个严重的健康问题，困扰着全球的医疗保健行业，导致每年在全球范围内有数十万人死亡。解决这个问题需要发现和开发新的抗菌剂。在这项研究中，我们发现了新型的 6-(1-取代吡咯-2-基)-三嗪类化合物，这些化合物能够有效地抑制 的生长，无论其耐甲氧西林状态如何，其最低抑菌浓度（MIC）值低至 1 μM。这些化合物的抗菌活性关键在于存在一个单咪唑取代基。一些化合物还抑制了几种非结核分枝杆菌。我们已经证明，这些分子是有效的抑菌剂，并且在相关浓度下对哺乳动物细胞没有毒性。进一步将这些化合物开发为新型抗菌药物，将旨在扩大我们的抗生素武器库。
