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Candidiasis is considered an emerging public health concern because of the occurrence of drug-resistant <i>Candida</i> strains and the lack of an available structurally diverse antifungal drug armamentarium. The indole alkaloid globospiramine from the anticandidal Philippine medicinal plant <i>Voacanga globosa</i> exhibits a variety of biological activities; however, its antifungal properties remain to be explored. In this study, we report the in vitro anticandidal activities of globospiramine against two clinically relevant <i>Candida</i> species (<i>C. albicans</i> and <i>C. tropicalis</i>) and the exploration of its possible target proteins using in silico methods. Thus, the colony-forming unit (CFU) viability assay revealed time- and concentration-dependent anticandidal effects of the alkaloid along with a decrease in the number of viable CFUs by almost 50% at 60 min after treatment. The results of the MIC and MFC assays indicated inhibitory and fungicidal effects of globospiramine against <i>C. albicans</i> (MIC = 8 µg/mL; MFC = 8 µg/mL) and potential fungistatic effects against <i>C. tropicalis</i> at lower concentrations (MIC = 4 µg/mL; MFC > 64 µg/mL). The FAM-FLICA poly-caspase assay showed metacaspase activation in <i>C. albicans</i> cells at concentrations of 16 and 8 µg/mL, which agreed well with the MIC and MFC values. Molecular docking and molecular dynamics simulation experiments suggested globospiramine to bind strongly with 1,3-β-glucan synthase and Als3 adhesin—enzymes indirectly involved in apoptosis-driven candidal inhibition.