Coumaric acid analogues inhibit growth and melanin biosynthesis in Cryptococcus neoformans and potentialize amphotericin B antifungal activity.

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
Lidiane OliveiraRenata C Pascon

Abstract

Fungal infections are on the rise, since the imunocompromised population is increasing due to AIDS/HIV, organ transplant and chemotherapy. Many environmental and pathogenic fungi are able to accomplish melanin biosynthesis as a virulence factor to promote host invasion. Melanized cells are more resistant to radiation, oxidative and osmotic stresses; also melanin confers an advantage in vivo, since melanized cells are more resistant to phagocytic engulfment and oxidative stress caused by the host defense cells and by some antifungal drugs, such as fluconazole (FCZ) and amphotericin B (AmB). Brown, red or black melanin pigments can be produced by the polyketide pathway (DHN-melanin) or from dihydroxyphenols, such as L-DOPA (L-3,4-dihydroxyphenylalanine) and L-tyrosine by polyphenoloxidases. Among several pathogenic fungi, Cryptococcus neoformans is a melanized yeast that causes pneumonia and meningoencephalitis in immunocompromised patients. The knockout of the laccase genes or other interruptions on melanin biosynthetic pathway generates cryptococcal strains with attenuated virulence in an animal model. In this study 16 analogues of coumaric and cinnamic acid were evaluated as possible tyrosinase inhibitors. We have identified s...Continue Reading

Citations

May 12, 2021·Antimicrobial Agents and Chemotherapy·Daiane HeidrichMaria Lúcia Scroferneker
Aug 9, 2021·European Journal of Medicinal Chemistry·Jin LiGuan Wang

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