Yano Masahide, Lawson-Rulli Jessica M, Coates Reilly M, Heldring Jennifer, Miller Marvin J, Liu Rui
Microbiology, Hsiri Therapeutics, Inc, Media, PA, 19063, USA.
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, 46556, USA.
Eur J Med Chem Rep. 2024 Aug;11. doi: 10.1016/j.ejmcr.2024.100147. Epub 2024 Mar 17.
Globally, millions of infections that are resistant to antimicrobial agents are reported annually, leading to more than 700,000 fatalities. Among all, challenges arise particularly from nontuberculosis mycobacterial (NTM) and Gram-negative bacteria, as they exhibit limited treatment options in light of increasing reports of multi-drug resistant strains. Clofazimine (CFZ) is an antimycobacterial medication used to treat leprosy, and it is also known for its side effect of inducing skin pigmentation. The use of CFZ and its analogues against a broad range of Gram-negative bacteria has not been extensively investigated. In this study, we designed, synthesized and studied 11 CFZ analogues and identified examples with comparable or improved anti-bacterial activity relative to that of CFZ itself. This is the first report demonstrating activity of CFZ and its analogues against species. The results of these studies may facilitate the development of CFZ analogues with limited side effects in humans.
在全球范围内，每年报告有数百万例对抗菌药物耐药的感染病例，导致70多万人死亡。其中，挑战尤其来自非结核分枝杆菌（NTM）和革兰氏阴性菌，因为随着多药耐药菌株报告的增加，它们的治疗选择有限。氯法齐明（CFZ）是一种用于治疗麻风病的抗分枝杆菌药物，它还以引起皮肤色素沉着的副作用而闻名。CFZ及其类似物对多种革兰氏阴性菌的应用尚未得到广泛研究。在本研究中，我们设计、合成并研究了11种CFZ类似物，并鉴定出了与CFZ本身相比具有相当或更好抗菌活性的实例。这是第一份证明CFZ及其类似物对[具体物种]具有活性的报告。这些研究结果可能有助于开发对人类副作用有限的CFZ类似物。
