Selenium-Containing (Hetero)Aryl Hybrids as Potential Antileishmanial Drug Candidates: In vitro Screening Against L. amazonensis

Leishmaniasis remains a significant global health concern, with current treatments relying on outdated drugs associated with high toxicity, lengthy administration, elevated costs, and drug resistance. Consequently, the urgent need for safer and more effective therapeutic options in leishmaniasis treatment persists. Previous research has highlighted selenium compounds as promising candidates for innovative leishmaniasis therapy. In light of this, a library of 10 selenium-containing diverse compounds was designed and evaluated in this study. The compounds were subjected to screening against L. amazonensis promastigotes, and their cytotoxicity was assessed in NIH/3T3 cells. Among the tested compounds, MRK-106 and MRK-108 displayed the highest potency against L. amazonensis promastigotes while demonstrating reduced cytotoxicity. Notably, MRK-106 and MRK-108 exhibited IC50 values of 3.97 µM, 4.23 µM, respectively, and most of the tested compounds showed low cytotoxicity in NIH/3T3 cells (CC50 > 200 µM). Although these results are promising, additional investigations focusing on intracellular amastigotes are required to determine the antileishmanial activity of the compounds. In conclusion, the identified selenium-containing compounds hold considerable potential as antileishmanial drug candidates and warrant further exploration in subsequent studies. These findings represent a significant step towards the development of safer and more effective therapies for leishmaniasis, addressing the pressing need for novel and improved treatments.