Manzano, J.A.H.; Brogi, S.; Calderone, V.; Macabeo, A.P.G.; Austriaco, N. Globospiramine Exhibits Inhibitory and Fungicidal Effects against Candida albicans via Apoptotic Mechanisms. Biomolecules2024, 14, 610.
Manzano, J.A.H.; Brogi, S.; Calderone, V.; Macabeo, A.P.G.; Austriaco, N. Globospiramine Exhibits Inhibitory and Fungicidal Effects against Candida albicans via Apoptotic Mechanisms. Biomolecules 2024, 14, 610.
Manzano, J.A.H.; Brogi, S.; Calderone, V.; Macabeo, A.P.G.; Austriaco, N. Globospiramine Exhibits Inhibitory and Fungicidal Effects against Candida albicans via Apoptotic Mechanisms. Biomolecules2024, 14, 610.
Manzano, J.A.H.; Brogi, S.; Calderone, V.; Macabeo, A.P.G.; Austriaco, N. Globospiramine Exhibits Inhibitory and Fungicidal Effects against Candida albicans via Apoptotic Mechanisms. Biomolecules 2024, 14, 610.
Abstract
Candidiasis is considered an emerging public health concern because of the occurrence of drug-resistant Candida strains and the lack of available structurally diverse antifungal drug armamentariums. The indole alkaloid globospiramine from the anticandidal Philippine medicinal plant Voacanga globosa exhibits a variety of biological activities; however, its antifungal properties remain to be explored. In this study, we report the in vitro antifungal activities of globospiramine against Candida albicans and Candida tropicalis and explore its possible target proteins using in silico methods. The colony-forming unit (CFU) viability assay revealed time- and concentration-dependent anticandidal effects of the alkaloid by decreasing almost 50% of the viable CFUs 60 min after treatment. Results of the MIC and MFC assays indicated inhibitory and fungicidal effects of globospiramine against C. albicans (MIC = 8 µg/mL; MFC = 4 µg/mL) and potential fungistatic effects against C. tropicalis at lower concentrations (MIC = 4 µg/mL; MFC > 64 µg/mL). The FAM-FLICA poly-caspase assay showed metacaspase activation in C. albicans cells at concentrations of 16 and 8 µg/mL, which agreed with the MIC and MFC values. Molecular docking and molecular dynamics simulation experiments indicated stable, strong binding of globospiramine with the target proteins 1,3-β-glucan synthase and Als3 adhesin enzymes, which are indirectly involved in apoptotic-driven candidal inhibition.
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