Nitulescu Georgiana, Margina Denisa, Zanfirescu Anca, Olaru Octavian Tudorel, Nitulescu George Mihai
Faculty of Pharmacy, "Carol Davila" University of Medicine and Pharmacy, Traian Vuia 6, 020956 Bucharest, Romania.
Pharmaceuticals (Basel). 2021 Apr 30;14(5):415. doi: 10.3390/ph14050415.
Increasingly ineffective antibiotics and rapid spread of multi- and pan-resistant bacteria represent a global health threat; hence, the need of developing new antimicrobial medicines. A first step in this direction is identifying new molecular targets, such as virulence factors. Sortase A represents a virulence factor essential for the pathogenesis of Gram-positive pathogens, some of which have a high risk for human health. We present here an exhaustive collection of sortases inhibitors grouped by relevant chemical features: vinyl sulfones, 3-aryl acrylic acids and derivatives, flavonoids, naphtoquinones, anthraquinones, indoles, pyrrolomycins, isoquinoline derivatives, aryl β-aminoethyl ketones, pyrazolethiones, pyridazinones, benzisothiazolinones, 2-phenyl-benzoxazole and 2-phenyl-benzofuran derivatives, thiadiazoles, triazolothiadiazoles, 2-(2-phenylhydrazinylidene)alkanoic acids, and 1,2,4-thiadiazolidine-3,5-dione. This review focuses on highlighting their structure-activity relationships, using the half maximal inhibitory concentration (IC), when available, as an indicator of each compound effect on a specific sortase. The information herein is useful for acquiring knowledge on diverse natural and synthetic sortases inhibitors scaffolds and for understanding the way their structural variations impact IC. It will hopefully be the inspiration for designing novel effective and safe sortase inhibitors in order to create new anti-infective compounds and to help overcoming the current worldwide antibiotic shortage.
日益失效的抗生素以及多重耐药菌和泛耐药菌的迅速传播构成了全球健康威胁；因此，开发新型抗菌药物迫在眉睫。朝着这个方向迈出的第一步是确定新的分子靶点，比如毒力因子。分选酶A是革兰氏阳性病原体致病机制中必不可少的一种毒力因子，其中一些对人类健康具有高风险。我们在此展示了按相关化学特征分类的分选酶抑制剂的详尽汇总：乙烯基砜、3-芳基丙烯酸及其衍生物、黄酮类化合物、萘醌、蒽醌、吲哚、吡咯霉素、异喹啉衍生物、芳基β-氨基乙基酮、吡唑硫酮、哒嗪酮、苯并异噻唑啉酮、2-苯基苯并恶唑和2-苯基苯并呋喃衍生物、噻二唑、三唑并噻二唑、2-(2-苯基肼叉)链烷酸以及1,2,4-噻二唑烷-3,5-二酮。本综述着重突出它们的构效关系，在可得的情况下，使用半数抑制浓度(IC)作为每种化合物对特定分选酶作用的指标。本文中的信息有助于获取关于各种天然和合成分选酶抑制剂支架的知识，并有助于理解其结构变化对IC的影响方式。希望它能为设计新型有效且安全的分选酶抑制剂提供灵感，从而创造新的抗感染化合物，并有助于克服当前全球范围内的抗生素短缺问题。
