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Antifungal activity of sustainable histone deacetylase inhibitors against planktonic cells and biofilms of Candida spp. and Cryptococcusneoformans
Univ Brasilia, Fac Med, Trop Med Ctr, Lab Dev Therapeut Innovat, Campus Darcy Ribeiro, BR-70910900 Brasilia, DF, Brazil.;Univ Brasilia, Fac Hlth Sci, Postgrad Program Pharmaceut Sci, Asa Norte, Campus Darcy Ribeiro, BR-70910900 Brasilia, DF, Brazil..
Univ Fed Ceara, Specialized Med Mycol Ctr, Dept Pathol & Legal Med, Postgrad Program Med Microbiol, Rua Cel Nunes Melo 1315, BR-60430275 Fortaleza, CE, Brazil..
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Glycoscience.ORCID iD: 0000-0002-3322-8621
Univ Brasilia, Fac Med, Postgrad Program Trop Med, Campus Darcy Ribeiro, BR-70910900 Brasilia, DF, Brazil..
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2023 (English)In: Medical Mycology, ISSN 1369-3786, E-ISSN 1460-2709, Vol. 61, no 8, article id myad073Article in journal (Refereed) Published
Abstract [en]

The limited therapeutic options for fungal infections and the increased incidence of fungal strains resistant to antifungal drugs, especially Candida spp., require the development of new antifungal drugs and strategies. Histone deacetylase inhibitors (HDACi), like vorinostat, have been studied in cancer treatment and have antifungal effects, acting alone or synergistically with classical antifungals. Here we investigated the antifungal activity of two novel sustainable HDACi (LDT compounds) based on vorinostat structure. Molecular docking simulation studies reveal that LDT compounds can bind to Class-I HDACs of Candida albicans, C. tropicalis, and Cryptococcus neoformans, which showed similar binding mode to vorinostat. LDT compounds showed moderate activity when tested alone against fungi but act synergistically with antifungal azoles against Candida spp. They reduced biofilm formation by more than 50% in C. albicans (4 µg/mL), with the main action in fungal filamentation. Cytotoxicity of the LDT compounds against RAW264.7 cells was evaluated and LDT536 demonstrated cytotoxicity only at the concentration of 200 µmol/L, while LDT537 showed IC50 values of 29.12 µmol/L. Our data indicated that these sustainable and inexpensive HDACi have potential antifungal and antibiofilm activities, with better results than vorinostat, although further studies are necessary to better understand the mechanism against fungal cells.

Place, publisher, year, edition, pages
Oxford University Press (OUP) , 2023. Vol. 61, no 8, article id myad073
Keywords [en]
antifungal activity, HDACi, hydroxamic acid, biofilm
National Category
Microbiology in the medical area
Identifiers
URN: urn:nbn:se:kth:diva-334763DOI: 10.1093/mmy/myad073ISI: 001046486100001PubMedID: 37553154OAI: oai:DiVA.org:kth-334763DiVA, id: diva2:1791164
Note

QC 20230824

Available from: 2023-08-24 Created: 2023-08-24 Last updated: 2023-08-24Bibliographically approved

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Kumar, RajenderSrivastava, Vaibhav

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