炭疽毒素小分子抑制剂

Small-molecule inhibitors of anthrax toxin

炭疽病是由炭疽芽孢杆菌(Bacillus anthracis)引起的恶性传染病,炭疽菌进入宿主后产生的炭疽毒素是感染者致死的主要原因。炭疽毒素含有2种具有酶催化活性的蛋白质——致死因子和水肿因子,以及1种共同的结合和转运蛋白质——炭疽保护性抗原,炭疽保护性抗原分别与上述两种因子组成致死毒素和水肿毒素。现阶段治疗炭疽病的主要药物为抗生素,但抗生素只能杀灭人体组织内的部分炭疽热孢子和细菌,不能抵抗孢子和细菌在体内产生的毒素,因而需要开发抑制炭疽毒素的新型药物。本文主要综述近年来国际上对靶向保护性抗原、致死因子和水肿因子的炭疽毒素小分子抑制剂的主要研究进展。

Anthrax is a malignant infectious disease caused by Bacillus anthracis spores,after entering the host Bacillus anthracis produces and releases anthrax toxin,which is the main cause leading to death of the host. The anthrax toxin is composed of two enzymatically active components：lethal factor（LF）and edema factor（EF）,and one shared receptor binding and translocation component：protective antigen（PA）. PA combined with LF is called lethal toxin（Le Tx）,while PA combined with EF called edema toxin（Ed Tx）. Currently,the main drugs for treating anthrax are antibiotics,but antibiotics can only kill part of anthrax spores and bacteria,and cannot inhibit the activity of anthrax toxin. So it is necessary to develop novel drugs for inhibiting anthrax toxin. This review summarizes the evolution of small-molecule inhibitors of anthrax toxin respectively targeting PA,LF and EF.