Levshin Igor B, Simonov Alexander Y, Lavrenov Sergey N, Panov Alexey A, Grammatikova Natalia E, Alexandrov Alexander A, Ghazy Eslam S M O, Savin Nikita A, Gorelkin Peter V, Erofeev Alexander S, Polshakov Vladimir I
Gause Institute of New Antibiotics, 11 B. Pirogovskaya Street, 119021 Moscow, Russia.
Bach Institute of Biochemistry, Federal Research Center of Biotechnology of the RAS, 119071 Moscow, Russia.
Pharmaceuticals (Basel). 2022 May 1;15(5):563. doi: 10.3390/ph15050563.
Novel derivatives of Mycosidine (3,5-substituted thiazolidine-2,4-diones) are synthesized by Knoevenagel condensation and reactions of thiazolidines with chloroformates or halo-acetic acid esters. Furthermore, 5-Arylidene-2,4-thiazolidinediones and their 2-thioxo analogs containing halogen and hydroxy groups or di(benzyloxy) substituents in 5-benzylidene moiety are tested for antifungal activity in vitro. Some of the synthesized compounds exhibit high antifungal activity, both fungistatic and fungicidal, and lead to morphological changes in the yeast cell wall. Based on the use of limited proteomic screening and toxicity analysis in mutants, we show that Mycosidine activity is associated with glucose transport. This suggests that this first-in-class antifungal drug has a novel mechanism of action that deserves further study.
通过克诺文纳格尔缩合反应以及噻唑烷与氯甲酸酯或卤代乙酸酯的反应合成了霉菌素（3,5-取代噻唑烷-2,4-二酮）的新型衍生物。此外，还对5-亚芳基-2,4-噻唑烷二酮及其在5-亚苄基部分含有卤素和羟基或二（苄氧基）取代基的2-硫代类似物进行了体外抗真菌活性测试。一些合成化合物表现出高抗真菌活性，兼具抑菌和杀菌作用，并导致酵母细胞壁发生形态变化。基于在突变体中使用有限的蛋白质组学筛选和毒性分析，我们表明霉菌素活性与葡萄糖转运有关。这表明这种一流的抗真菌药物具有值得进一步研究的新型作用机制。
