Introduction. In the modern world, more attention is paid to the problem of increasing cases of mycosis. In October 2022, the World Health Organization (WHO) published the first fungal priority pathogens list which constitute the greatest danger to human health. Among mycotic infections, one of the leading positions in frequency is occupied by various forms of candidiasis. The WHO has classified Candida albicans as a critical priority group. Therefore, the search for new effective antimycotics is relevant. A new derivative of 1,3,4-thiadiazole was synthesized at Saint-Petersburg State Chemical and Pharmaceutical University. In vitro experiments, it was shown that it has a wide spectrum of antifungal activity in effectiveness comparable to voriconazole.Aim. To evaluate the antifungal activity of 2-[(1Z)-1-(3,5-diphenyl-1,3,4-thiadiazol-2(3H)-ylidene)methyl]-3,5-diphenyl-1,3,4-thiadiazole-3-ium (thiadiazole derivative, TD) chloride drug substance in non-invasive bowel candidiasis and acute septicemia (sepsis) models caused by C. albicans.Materials and methods. Simulations of non-invasive intestinal candidiasis were performed by infecting BALB/c mice with candida with free access to a drinking bottle containing C. albicans yeast cells suspension. Previously, dysbiosis was caused in animals by adding a solution of antibiotics (vancomycin, clindamycin, gentamicin) in drinking water. Simulations of C. albicans-induced acute septicemia were performed by infecting BALB/c mice with intravenous yeast culture suspension. After the mice were infected, the test substance and the comparators Voriconazole and Fluconazole were administered intragastrically once daily. At the end of the experiment, the number of fallen animals were estimated and microbiological examination of internal organs was carried out.Results and discussion. It was shown that the number of yeast cells secreted from the large and small intestines in mice with non-invasive intestinal candidiasis after administration of a new thiadiazole derivative at all doses tested (1, 5, 10 mg/kg) were significantly reduced compared with control group No. 6 without treatment. At 10 mg/kg, the test substance demonstrated anticandidosis effects at the level of comparators drugs, Voriconazole and Fluconazole. In mice with septicemia, mortality also depended from the dose of the thiadiazole derivative, but only 10 mg/kg proved to be an effective dose.Conclusion. The study revealed that the new thiadiazol derivative 2-[(1Z)-1-(3,5-diphenyl-1,3,4-thiadiazol-2(3H)-ylidene) methyl]-3,5-diphenyl-1,3,4-thiadiazole-3-ium showed antifungal activity against Candida albicans in the model of non-invasive intestinal candidiasis and the model of septicemia (sepsis). At 10 mg/kg, TD was found to be active at the level of comparators, Voriconazole and Fluconazole.
