Effect of Mn(II) and Co(II) on Anti-Candida Metabolite Production by Aspergillus sp. an Endophyte Isolated from Dizygostemon riparius (Plantaginaceae)

<b>Background/Objectives</b>: This study evaluates the effect of Mn(II) and Co(II) ions on the production of anti-<i>Candida</i> metabolites by the endophytic fungus Aspergillus sp., isolated from <i>Dizygostemon riparius</i>. The objective was to identify metal-induced secondary metabolites with antifungal potential against drug-resistant <i>Candida</i> species. <b>Methods</b>: <i>Aspergillus</i> sp. was cultivated in Czapek agar supplemented with MnCl₂ (400 µM) or CoCl₂ (200 µM). Metabolite profiles were analyzed using UHPLC-DAD and LC-ESI-HRMS, followed by structural elucidation via NMR. Antifungal and biofilm inhibition activities were tested against <i>Candida albicans</i> and <i>Candida parapsilosis</i>. Toxicity was assessed using <i>Tenebrio molitor</i> larvae. <b>Results</b>: Key metabolites, including pyrophen, penicillquei B, and fonsecinone B, demonstrated antifungal activity with MIC values of 4.37-280.61 µg/mL. Fonsecinone B exhibited superior biofilm inhibition, surpassing fluconazole in reducing biofilm biomass and viability. In vivo assays showed low toxicity, with survival rates above 80% at 2× MIC/kg. <b>Conclusions</b>: Mn(II) and Co(II) significantly modulated the production of antifungal metabolites in <i>Aspergillus</i> sp. Fonsecinone B emerged as a promising candidate for antifungal therapy due to its potent activity and low toxicity. These findings support further investigation into the therapeutic potential of metal-induced fungal metabolites for combating drug-resistant <i>Candida</i> infections.