Antifungal profile of menadione tethered to 1H-1,2,3-triazolyl-selenoester: synthesis, in vitro and in silico analyses

Invasive Candidiasis infections are a clinical challenge, with limited effective therapeutic agents and increasing resistance. The discovery of new antifungal agents is urgently required. Here, we developed a new series of 2-methyl-1,4-naphthoquinone (Menadione) Tethered to 1H-1,2,3-triazolyl-selenoester in good yields, which exhibit antifungal potential activity against Candida species. Antifungal and antibiofilm activities for the twenty-one compounds were performed in vitro against Candida spp and exhibited inhibitory effects at different concentrations for several Candida species. Two compounds showed strong inhibitory effects, with fungicidal activity at 16 and 32 μg/mL, respectively, against planktonic cells and biofilms of Candida glabrata. In silico studies were conducted to determine the binding energies against BonFIRE spectral images of antifungal protein targets, and provided stereo electronic, pharmacokinetic and toxicological profiles. The analysis through molecular docking with CYP51 and Hsp90 highlighted the inhibitory potential of the compounds in comparison to itraconazole and radicicol, and further underscored the favorable pharmacokinetic profile for all molecules, characterized by a low toxicity profile. We therefore concluded that two compounds especially exhibited potent antifungal activity against C. glabrata.