Cargando…

Increasing Susceptibility of Drug-Resistant Candida albicans to Fluconazole and Terbinafine by 2(5H)-Furanone Derivative

The frequency of mycoses caused by drug-resistant fungal pathogen Candida albicans has increased drastically over the last two decades. The spread of drug-resistant strains, along with the limitations of currently available antifungals, complicates the management of fungal infections, thereby repres...

Descripción completa

Detalles Bibliográficos
Autores principales: Sharafutdinov, Irshad S., Ozhegov, Georgii D., Sabirova, Alina E., Novikova, Valentina V., Lisovskaya, Svetlana A., Khabibrakhmanova, Alsu M., Kurbangalieva, Almira R., Bogachev, Mikhail I., Kayumov, Airat R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036972/
https://www.ncbi.nlm.nih.gov/pubmed/32024254
http://dx.doi.org/10.3390/molecules25030642
_version_ 1783500318493900800
author Sharafutdinov, Irshad S.
Ozhegov, Georgii D.
Sabirova, Alina E.
Novikova, Valentina V.
Lisovskaya, Svetlana A.
Khabibrakhmanova, Alsu M.
Kurbangalieva, Almira R.
Bogachev, Mikhail I.
Kayumov, Airat R.
author_facet Sharafutdinov, Irshad S.
Ozhegov, Georgii D.
Sabirova, Alina E.
Novikova, Valentina V.
Lisovskaya, Svetlana A.
Khabibrakhmanova, Alsu M.
Kurbangalieva, Almira R.
Bogachev, Mikhail I.
Kayumov, Airat R.
author_sort Sharafutdinov, Irshad S.
collection PubMed
description The frequency of mycoses caused by drug-resistant fungal pathogen Candida albicans has increased drastically over the last two decades. The spread of drug-resistant strains, along with the limitations of currently available antifungals, complicates the management of fungal infections, thereby representing great challenges for clinical healthcare. Among various antimicrobial pharmacophores, 2(5H)-furanone derivatives have demonstrated antimicrobial, antifungal, and antibiofilm activities. In this study, we report the antifungal activity of the 2(5H)-furanone derivative F105, consisting of three pharmacophores, namely chlorinated 2(5H)-furanone, sulfonyl group, and l-menthol moiety. Although exhibiting moderate antifungal activity alone with the minimum inhibitory concentration (MIC) values of 32–256 μg/mL, F105 potentiates the activity of fluconazole and terbinafine with fractional inhibitory concentration index (FICI) values of 0.27–0.50. Thus, 16 μg/mL of F105 reduced the MICs of these antifungals against fluconazole-resistant C. albicans isolates four-fold, achieving similar values as for the intermediately susceptible phenotype. Confocal laser scanning microscopy revealed that the fluorescent 2(5H)-furanone derivative F145 was also able to penetrate through biofilms formed by C. albicans. Indeed, in the presence of F105, even sub-MIC concentrations of both fluconazole and terbinafine led to significant reduction of C. albicans CFUs in the mature biofilm. Thus, F105 appears to be a promising candidate for the development of novel antifungal agents as well as enhancers of current antifungal agents, particularly for the treatment of drug-resistant C. albicans infections.
format Online
Article
Text
id pubmed-7036972
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-70369722020-03-11 Increasing Susceptibility of Drug-Resistant Candida albicans to Fluconazole and Terbinafine by 2(5H)-Furanone Derivative Sharafutdinov, Irshad S. Ozhegov, Georgii D. Sabirova, Alina E. Novikova, Valentina V. Lisovskaya, Svetlana A. Khabibrakhmanova, Alsu M. Kurbangalieva, Almira R. Bogachev, Mikhail I. Kayumov, Airat R. Molecules Article The frequency of mycoses caused by drug-resistant fungal pathogen Candida albicans has increased drastically over the last two decades. The spread of drug-resistant strains, along with the limitations of currently available antifungals, complicates the management of fungal infections, thereby representing great challenges for clinical healthcare. Among various antimicrobial pharmacophores, 2(5H)-furanone derivatives have demonstrated antimicrobial, antifungal, and antibiofilm activities. In this study, we report the antifungal activity of the 2(5H)-furanone derivative F105, consisting of three pharmacophores, namely chlorinated 2(5H)-furanone, sulfonyl group, and l-menthol moiety. Although exhibiting moderate antifungal activity alone with the minimum inhibitory concentration (MIC) values of 32–256 μg/mL, F105 potentiates the activity of fluconazole and terbinafine with fractional inhibitory concentration index (FICI) values of 0.27–0.50. Thus, 16 μg/mL of F105 reduced the MICs of these antifungals against fluconazole-resistant C. albicans isolates four-fold, achieving similar values as for the intermediately susceptible phenotype. Confocal laser scanning microscopy revealed that the fluorescent 2(5H)-furanone derivative F145 was also able to penetrate through biofilms formed by C. albicans. Indeed, in the presence of F105, even sub-MIC concentrations of both fluconazole and terbinafine led to significant reduction of C. albicans CFUs in the mature biofilm. Thus, F105 appears to be a promising candidate for the development of novel antifungal agents as well as enhancers of current antifungal agents, particularly for the treatment of drug-resistant C. albicans infections. MDPI 2020-02-02 /pmc/articles/PMC7036972/ /pubmed/32024254 http://dx.doi.org/10.3390/molecules25030642 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sharafutdinov, Irshad S.
Ozhegov, Georgii D.
Sabirova, Alina E.
Novikova, Valentina V.
Lisovskaya, Svetlana A.
Khabibrakhmanova, Alsu M.
Kurbangalieva, Almira R.
Bogachev, Mikhail I.
Kayumov, Airat R.
Increasing Susceptibility of Drug-Resistant Candida albicans to Fluconazole and Terbinafine by 2(5H)-Furanone Derivative
title Increasing Susceptibility of Drug-Resistant Candida albicans to Fluconazole and Terbinafine by 2(5H)-Furanone Derivative
title_full Increasing Susceptibility of Drug-Resistant Candida albicans to Fluconazole and Terbinafine by 2(5H)-Furanone Derivative
title_fullStr Increasing Susceptibility of Drug-Resistant Candida albicans to Fluconazole and Terbinafine by 2(5H)-Furanone Derivative
title_full_unstemmed Increasing Susceptibility of Drug-Resistant Candida albicans to Fluconazole and Terbinafine by 2(5H)-Furanone Derivative
title_short Increasing Susceptibility of Drug-Resistant Candida albicans to Fluconazole and Terbinafine by 2(5H)-Furanone Derivative
title_sort increasing susceptibility of drug-resistant candida albicans to fluconazole and terbinafine by 2(5h)-furanone derivative
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036972/
https://www.ncbi.nlm.nih.gov/pubmed/32024254
http://dx.doi.org/10.3390/molecules25030642
work_keys_str_mv AT sharafutdinovirshads increasingsusceptibilityofdrugresistantcandidaalbicanstofluconazoleandterbinafineby25hfuranonederivative
AT ozhegovgeorgiid increasingsusceptibilityofdrugresistantcandidaalbicanstofluconazoleandterbinafineby25hfuranonederivative
AT sabirovaalinae increasingsusceptibilityofdrugresistantcandidaalbicanstofluconazoleandterbinafineby25hfuranonederivative
AT novikovavalentinav increasingsusceptibilityofdrugresistantcandidaalbicanstofluconazoleandterbinafineby25hfuranonederivative
AT lisovskayasvetlanaa increasingsusceptibilityofdrugresistantcandidaalbicanstofluconazoleandterbinafineby25hfuranonederivative
AT khabibrakhmanovaalsum increasingsusceptibilityofdrugresistantcandidaalbicanstofluconazoleandterbinafineby25hfuranonederivative
AT kurbangalievaalmirar increasingsusceptibilityofdrugresistantcandidaalbicanstofluconazoleandterbinafineby25hfuranonederivative
AT bogachevmikhaili increasingsusceptibilityofdrugresistantcandidaalbicanstofluconazoleandterbinafineby25hfuranonederivative
AT kayumovairatr increasingsusceptibilityofdrugresistantcandidaalbicanstofluconazoleandterbinafineby25hfuranonederivative