Candidiasis: the problem of finding new etiotropic drugs among organic synthesis products

Abstract

1043 compounds - products of organic synthesis were screened for antifungal activity on the type strain C. albicans NCTC 885-653 in planktonic culture. In-depth studies of substances with high activity against typical strains of Candida spp. and clinical isolates to identify lead compounds, including on a biofilm model were done. 3 substances were identified that exhibit high antifungal activity (MIC50 - 1.0-2.0; MIC90 - 7.8-31.2), exceeding the effect of the reference drug fluconazole. Thus, representatives of new chemical groups with antifungal activity were identified. A methodology has been developed for searching for compounds with antifungal activity among products of organic synthesis, based on the use of a combination of theoretical, physicochemical, and biological methods. An algorithm for the early stages of preclinical studies of the presence of antifungal activity in newly synthesized compounds using microbiological methods is proposed. It including screening studies for typical strains of yeast micromycetes, in-depth studies of clinical isolates to study the cumulative indicators of sensitivity of a population of strains, and determination of the antifungal activity of compounds on a biofilm model.