Mikrobiol. Z. 2019; 81(2):73-83. Ukrainian.
Antifungal Activity of Arylaliphatic Aminopropanol Derivative 1-[4-(1,1,3,3-Tetramethylbutyl)phenoxy]-
Institute of Pharmacology and Toxicology, NAMS of Ukraine
14 A. Tsedika Str., Kyiv, 03057, Ukraine
Aim. The purpose of the work was to investigate the antifungal activity of the arylaliphatic aminopropanol derivative 1-[4-(1,1,3,3-tetramethylbutyl)phenoxy]-3-(N-benzyl-4-methylpiperidinium)-2-propanol chloride (KVM-204) against yeasts, filamentous fungi and dermatophytes. Methods. The susceptibility of the fungi to the compound KVM-204 was determined by two-fold broth dilution method and evaluated by the means of the minimum inhibitory concentration (MIC). The determination of cytomorphological features of filamentous fungi under the action of compound was carried out by light microscopy. The effect of KVM-204 on the germ-tubes formation was investigated against fungi the genus Candida by the method of Larone. Results. The compound KVM-204 possess a wide spectrum of anti-candida activity, the inhibitory effect of compound is close to fluconazole and itraconazole (except Candida parapsilosis). It has been established that the arylaliphatic aminopropanol derivative possess antifungal activity against Trichophyton mentagrophytes var. gypseum, according to the MIC, compound is not inferior to fluconazole. Exposure of arylaliphatic aminopropanol derivative KVM-204 at 1.0 MIC on filamentous fungi causes significant cytomorphological alterations in the cell wall of the microorganisms. Compound KVM-204 at 1.0 MIC and 5.0 MIC inhibits the formation of germ-tubes by Candida albicans, the action of the compound is comparable to that of amphotericin B. Conclusions. Studies on antifungal activity have shown that the compound KVM-204 possess a pronounced anticandida effect. The KVM-204 also alters the morphology of filamentous fungi and inhibits the formation of germ-tubes by Candida spp., influencing the pathogenicity of yeasts.
Keywords: antifungal activity, arylaliphatic aminopropanol derivative, dermatophytes, fungi the genus Candida, filamentous fungi.
Full text (PDF, in Ukrainian)
- Köhler JR, Casadevall A, Perfect J.The spectrum of fungi that infects humans. Cold Spring Harb Perspect Med. 2015; 5(1):a019273. https://doi.org/10.1101/cshperspect.a019273
- Yelinov NP. [Candida species and candidemia. The problem's condition (Survey)]. Problemy meditsinskoy mikologii. 2001; 3(1):4-15. Russian.
- Kaur R, Mehra B, Dhakad MS, Goyal R, Bhalla P, Dewan R. Fungal opportunistic pneumonias in HIV/AIDS patients: an Indian tertiary care experience. J. Clin. Diagn. Res. 2017; 11(2):DC14–DC19. https://doi.org/10.7860/JCDR/2017/24219.9277
- Giri SA, Kindo AJ. A review of Candida species causing bloods tream in fection. Indian Journal of Medical Microbiology. 2012; 30(3):270-278. https://doi.org/10.4103/0255-0857.99484
- Perlroth J, Choi B, Spellberg B.Nosocomial fungal infections: epidemiology, diagnosis, and treatment. Med Mycol. 2007; 45(4):321-346. https://doi.org/10.1080/13693780701218689
- Dronova M, Vrynchanu N, Varbanets L, Korotkiy Y, Brovarska O. Arylaliphatic aminoalcohol derivative KVM-194 affects E. coli lipoposaccharide composition. Farmacia. 2015; 63(4):586-592.
- Volyansky YL, Hrytsenko IS, Shyrobokov VP. [The study of the specific activity of antimicrobial drugs: guideline of MoH of Ukraine]. Kyiv: Health Publisher (Zdorovja); 2004. Ukrainian.
- Antimicrobial wild type distributions of microorganisms. Basel: The European Committee on Antimicrobial Susceptibility Testing – EUCAST. c2007 – available from: https://mic.eucast.org/Eucast2/.
- Vrynchanu NO, Burmaka OV, Dronova ML, Dudikova DM, Suvorova ZS. [The study of the specific activity of antifungal drugs: guideline]. Kyiv: MoH of Ukraine, PE "The State Expert Center of the MoH of Ukraine"; 2016. Ukrainian.
- Matare T, Nziramasanga P, Gwanzura L, Robertson V. Experimental germ tube induction in Candida albicans: an evaluation of the effect of sodium bicarbonate on morphogenesis and comparison with pooled human serum. Hindawi. Biomed Res Int. 2017; 2017:1976273.
- Bremm KD, Hawkins J, Plempel M, Berg D. Influence of azole compounds on adhesion, germ tube formation and virulence of C. albicans in cell cultures and infected animals. Candida and Candidamycosis. 1991; 50:97-100. https://doi.org/10.1007/978-1-4684-5910-4_13
- Belousova TA, Goryachkina MV. [Foot mycosis: a rational choice of therapy]. RMZh. 2011; 19(11):688–692. Russian.
- Sutton DA, Fothergill AW, Rinaldi MG. [Guide to clinically significant fungi]. Dorozhkova IR, ed. Moscow: Mir; 2001. Russian.
- Santos DA, Hamdan JS. Evaluation of broth microdilution antifungal susceptibility testing conditions for Trichophyton rubrum. J. Clin. Microbiol. 2005; 43(4):1917-1920. https://doi.org/10.1128/JCM.43.4.1917-1920.2005
- Gupta AK, Ahmad I, Summerbell RC. Fungicidal activities of commonly used disinfectants and antifungal pharmaceutical spray preparations against clinical strains of Aspergillus and Candida species. Medical Mycology. 2002; 40:201–208. https://doi.org/10.1080/mmy.18.104.22.168
- Brand A. Hyphal growth in human fungal pathogens and its role in virulence. Int. J. Microbiol. 2012; 2012:517529. https://doi.org/10.1155/2012/517529
- Van't Wout JW, Meynaar I, Linde I, Poell R, Mattie H, Van Furth R. Effect of amphotericin B, fluconazole and itraconazole on intracellular Candida albicans and germ tube development in macrophages. J. Antimicrob. Chemother. 1990; 25(5):803–11. https://doi.org/10.1093/jac/25.5.803