Faculty of Pharmacy, "Iuliu Hațieganu" University of Medicine and Pharmacy, 8 Victor Babes St, 400012 Cluj-Napoca, Romania.
Department of Microbiology, Faculty of Biology, University of Bucharest, 1-3 Portocalelor Street, 60101 Bucharest, Romania.
Molecules. 2017 Oct 27;22(11):1827. doi: 10.3390/molecules22111827.
Sortase A inhibition is a well establish strategy for decreasing bacterial virulence by affecting numerous key processes that control biofilm formation, host cell entry, evasion and suppression of the immune response and acquisition of essential nutrients. A meta-analysis of structures known to act as Sortase A inhibitors provided the starting point for identifying a new potential scaffold. Based on this template a series of new potential Sortase A inhibitors, that contain the 2-phenylthiazole moiety, were synthesized. The physicochemical characterisation confirmed the identity of the proposed structures. Antibacterial activity evaluation showed that the new compounds have a reduced activity against bacterial cell viability. However, the compounds prevent biofilm formation at very low concentrations, especially in the case of . Molecular docking studies performed estimate that this is most likely due to the inhibition of Sortase A. The new compounds could be used as add-on therapies together with known antibacterial agents in order to combat multidrug-resistance enterococcal infections.
通过影响控制生物膜形成、宿主细胞进入、逃避和抑制免疫反应以及获取必需营养物质的众多关键过程，金黄色葡萄球菌表面蛋白 A （Sortase A） 抑制已成为降低细菌毒力的一种成熟策略。对已知作为 Sortase A 抑制剂的结构进行的荟萃分析为确定新的潜在支架提供了起点。基于该模板，设计并合成了一系列包含 2-苯基噻唑部分的新的潜在 Sortase A 抑制剂。物理化学特性分析证实了所提出结构的身份。抗菌活性评估表明，新化合物对细菌细胞活力的活性降低。然而，这些化合物在非常低的浓度下可以防止生物膜的形成，特别是在. 进行的分子对接研究估计，这很可能是由于 Sortase A 的抑制。新化合物可与已知的抗菌剂一起用作附加疗法，以对抗耐多药肠球菌感染。
