Delpe-Acharige Anjana, Zhang Man, Eschliman Kayla, Dalecki Alex, Covarrubias-Zambrano Obdulia, Minjarez-Almeida Azriel, Shrestha Tejaswi, Lewis Tanji, Al-Ibrahim Fatimah, Leonard Sophia, Roberts Riana, Tebeje Anteneh, Malalasekera Aruni P, Wang Hongwang, Kalubowilage Madumali, Wolschendorf Frank, Kutsch Olaf, Bossmann Stefan H
Department of Chemistry, Kansas State University, Manhattan, Kansas 66506, United States.
Department of Medicine, University of Alabama at Birmingham, 845 19th Street S, Birmingham, Alabama 35294, United States.
ACS Omega. 2021 Feb 22;6(9):6088-6099. doi: 10.1021/acsomega.0c04513. eCollection 2021 Mar 9.
A novel series of copper-activatable drugs intended for use against methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) were synthesized, characterized, and tested against the MSSA strain Newman and the MRSA Lac strain (a USA300 strain), respectively. These drugs feature an NNSN structural motif, which enables the binding of copper. In the absence of copper, no activity against MSSA and MRSA at realistic drug concentrations was observed. Although none of the novel drug candidates exhibits a stereocenter, sub-micromolar activities against SA Newman and micromolar activities against SA Lac were observed in the presence, but not in the absence, of bioavailable copper. Copper influx is a component of cellular response to bacterial infections, which is often described as nutritional immunity.
合成了一系列新型的可被铜激活的药物，旨在用于对抗甲氧西林敏感金黄色葡萄球菌（MSSA）和耐甲氧西林金黄色葡萄球菌（MRSA），并分别对MSSA菌株Newman和MRSA Lac菌株（一种USA300菌株）进行了表征和测试。这些药物具有NNSN结构基序，能够结合铜。在没有铜的情况下，在实际药物浓度下未观察到对MSSA和MRSA的活性。尽管没有一种新型候选药物具有立体中心，但在存在可生物利用铜的情况下，观察到对SA Newman有亚微摩尔活性，对SA Lac有微摩尔活性，而在没有铜的情况下则未观察到。铜流入是细胞对细菌感染反应的一个组成部分，这通常被描述为营养免疫。
