Repurposing of Clomiphene Citrate and Its Antileishmanial and Antifungal Activities: In Silico and In Vitro Studies.

This study investigated the repurposing potential of clomiphene citrate as a topical therapeutic candidate for tegumentary leishmaniasis (TL) and candidiasis. Comparative in silico analyses were performed to evaluate absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties in comparison with meglumine antimoniate and amphotericin B. In addition, molecular docking was conducted to investigate the interaction of clomiphene with Leishmania spp. arginase and the Sap5 protease of Candida albicans. Clomiphene exhibited a favorable physicochemical profile, characterized by high lipophilicity, moderate skin permeability, and predicted oral bioavailability and intestinal absorption superior to those of the reference drugs. Toxicological predictions also indicated a lower systemic toxicity profile compared with conventional therapies. Molecular docking revealed favorable binding energies and interactions with key residues within the active sites of both targets. Experimental assays demonstrated that clomiphene inhibited the early stages of C. albicans biofilm formation and exhibited potent leishmanicidal activity against L. amazonensis promastigotes, with a high selectivity index in macrophages. Together, these findings indicate that clomiphene citrate represents a promising candidate for further investigation as a potential therapeutic agent against tegumentary leishmaniasis and candidiasis.