Antifungal Thiazolidines: Synthesis and Biological Evaluation of Mycosidine Congeners

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 Candida 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. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Authors
Levshin I.B.1 , Simonov A.Y.1 , Lavrenov S.N.1 , Panov A.A.1 , Grammatikova N.E.1 , Alexandrov A.A.2 , Ghazy E.S.M.O. 2, 3, 4 , Savin N.A.5 , Gorelkin P.V.5 , Erofeev A.S.5 , Polshakov V.I.6
Journal
Publisher
MDPI AG
Number of issue
5
Language
English
Status
Published
Number
563
Volume
15
Year
2022
Organizations
  • 1 Gause Institute of New Antibiotics, 11 B. Pirogovskaya Street, Moscow, 119021, Russian Federation
  • 2 Bach Institute of Biochemistry, Federal Research Center of Biotechnology of the RAS, Moscow, 119071, Russian Federation
  • 3 Institute of Biochemical Technology and Nanotechnology, Peoples’ Friendship University of Russia (RUDN), 6 Miklukho-Maklaya Street, Moscow, 117198, Russian Federation
  • 4 Department of Microbiology, Faculty of Pharmacy, Tanta University, Tanta, 31111, Egypt
  • 5 Department of Materials Science of Semiconductors and Dielectrics, National University of Science and Technology “MISiS”, 4 Leninsky Ave, Moscow, 119049, Russian Federation
  • 6 Faculty of Fundamental Medicine, Lomonosov Moscow State University, 27/1 Lomonosovsky Ave, Moscow, 119991, Russian Federation
Keywords
antifungal activity; cell wall; drug design; glucose transport; thiazolidine-2,4-dione
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