Production of More Potent Anti-Candida Labdane Diterpenes by Biotransformation Using Cunninghamella elegans

Author(s)

Sousa, Ingrid P. ; De Sousa Teixeira, Maria, V ; Freitas, Jolindo A. ; Ferreira, Antonio G. ; Pires, Loren M. ; Santos, Raquel A. ; Gomes Heleno, Vladimir Constantino ; Cardoso Furtado, Niege A. Jacometti

• Document type: Journal article
• Source: CHEMISTRY & BIODIVERSITY; v. 19, n. 3, p. 9-pg., 2022-02-19.

Abstract

Candida species are responsible for causing invasive candidiasis with high mortality rate and their resistance to available antifungal drugs is a major clinical challenge. Biotransformation process of the labdane diterpene ent-labd-8(17)-en-15,18-dioic acid (1) carried out with Cunninghamella elegans afforded five new derivatives (compounds 2-6). Unusual regioselective hydroxylation of the methyl group at the C-20 position of labdane-type diterpene was achieved and all compounds were subjected to cytotoxicity and antifungal evaluations. Compound 1 and its derivatives were not cytotoxic to normal (MCF-10A) and tumor (MCF-7) cell lines. Compounds 2 and 3 exhibited fungistatic activity against all tested Candida strains at lower concentrations than fluconazole. Both compounds also showed the strongest fungicidal activity against C. albicans, which is the most prevalent fungal agent involved in candidemia. (AU)

• FAPESP's process: 11/13630-7 - Chemical and pharmacological validation of extracts and active compounds of Copaifera species
• Grantee: Jairo Kenupp Bastos
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/25201-7 - In vitro studies of bioaccessibility, intestinal transportation and biotransformation of ent-hardwickiic and ent-polyalthic acids from Copaifera pubiflora and Copaifera duckei oil resins
• Grantee: Niege Araçari Jacometti Cardoso Furtado
• Support Opportunities: Regular Research Grants