Evaluation of antifungal potential of novel quaternary aryloxyethoxy dialkyl ammonium salts against Candida strains

V. B. Nastenko; V. P. Shyrobokov; V. P. Kovalchuk; Y. V. Korotkyi; N. O. Osypchuk

doi:10.15421/0226036

V. B. Nastenko Bogomolets National Medical University
V. P. Shyrobokov Bogomolets National Medical University
V. P. Kovalchuk Pirogov Vinnytsia National Medical University
Y. V. Korotkyi Institute of Organic Chemistry of NAS of Ukraine
N. O. Osypchuk Bogomolets National Medical University

Keywords: Candida krusei, Candida glabrata, Candida utilis, Candida parapsilosis, Candida tropicalis, Candida kefir, Candida lusitaniae, MIC, dialkyl ammonium salts.

Abstract

The spread of resistance to antimycotic drugs among C andida , microorganisms that play an important role as pathogens of fungal origin, is a serious problem for the modern medical system. The study aimed to investigate the antifungal properties of aryl acyclic amino alcohols. Previous studies selected ten preparations with the conventional names Kc2, Kc3, Kc14, Kc15, Kc16, Kc22, Kp4, Kp8, Kp18 and Kp19. The antifungal activity of fluconazole , a m photericin B, nystatin , and the surface antiseptics miramist i n and decamethoxin was studied. Among these drugs, amphotericin B demonstrated declared efficacy against all strains. Nystatin showed variable effects, and fluconazole showed low efficacy (MIC > 10 µg/ mL ), especially against Pichia kudriavzevii ( C andida krusei ) and Nakaseomyces glabratus ( C. glabrata ). Miramistin and decamethoxin had a moderate effect only against some species (MIC 3 – 5 µg/ mL ). Compounds Kc14, Kc15, Kc16, Kp8 and Kp18 showed exceptional activity in vitro , approaching the effic a cy of amphotericin B against C. parapsilosis , C. kefir , C. tropicalis and C. utilis . Kc22 demonstrated a broad spectrum of activity. Compounds Kc2, Kc3, Kp4 and Kp19 were more effective than fluconazole , miramistin and decamethoxine , showing similar effects to nystatin . The time-kill assay confirmed the concentration dependence, showing a fungistatic effect at ¼*MIC and a rapid bactericidal effect at 2*MIC. Although the mechanisms of action have not been studied, they are likely related to the disruption of membrane integrity and metabolic processes of fu n gal cells.

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