| Autor: |
Levshin IB; Gause Institute of New Antibiotics, 11 B. Pirogovskaya Street, 119021 Moscow, Russia., Simonov AY; Gause Institute of New Antibiotics, 11 B. Pirogovskaya Street, 119021 Moscow, Russia., Lavrenov SN; Gause Institute of New Antibiotics, 11 B. Pirogovskaya Street, 119021 Moscow, Russia., Panov AA; Gause Institute of New Antibiotics, 11 B. Pirogovskaya Street, 119021 Moscow, Russia., Grammatikova NE; Gause Institute of New Antibiotics, 11 B. Pirogovskaya Street, 119021 Moscow, Russia., Alexandrov AA; Bach Institute of Biochemistry, Federal Research Center of Biotechnology of the RAS, 119071 Moscow, Russia., Ghazy ESMO; Bach Institute of Biochemistry, Federal Research Center of Biotechnology of the RAS, 119071 Moscow, Russia.; Institute of Biochemical Technology and Nanotechnology, Peoples' Friendship University of Russia (RUDN), 6 Miklukho-Maklaya Street, 117198 Moscow, Russia.; Department of Microbiology, Faculty of Pharmacy, Tanta University, Tanta 31111, Egypt., Savin NA; Research Laboratory of Biophysics, National University of Science and Technology 'MISiS', 4 Leninsky Ave., 119049 Moscow, Russia., Gorelkin PV; Research Laboratory of Biophysics, National University of Science and Technology 'MISiS', 4 Leninsky Ave., 119049 Moscow, Russia., Erofeev AS; Research Laboratory of Biophysics, National University of Science and Technology 'MISiS', 4 Leninsky Ave., 119049 Moscow, Russia., Polshakov VI; Faculty of Fundamental Medicine, Lomonosov Moscow State University, 27/1 Lomonosovsky Ave., 119991 Moscow, Russia. |
| Abstrakt: |
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. |
