Natural Product-Based Antileishmanial Drug Discovery – Preliminary in silico study

Leishmaniasis is a neglected tropical disease caused by Leishmania parasites and transmitted through the bite of infected sand flies. Depending on their clinical manifestations, leishmaniases are classified into three major forms: cutaneous, mucocutaneous, and visceral, the latter being fatal if left untreated. In addition to its impact on human health, leishmaniasis is also a significant veterinary concern, particularly in dogs infected with L. infantum, which serve as the main reservoir hosts. In the context of global warming, the geographical expansion of sand fly vectors has increased the risk of disease spread, further emphasizing the importance of effective control strategies. Despite this growing threat, safe, effective, and affordable treatments for parasitic infections remain limited. Currently available antileishmanial drugs are associated with major drawbacks, including toxicity, high cost, prolonged treatment regimens, and the emergence of drug resistance. These limitations have driven extensive efforts toward the discovery and development of novel antileishmanial agents with improved safety and efficacy profiles. Among the promising candidates, steroid-based compounds have attracted considerable attention from pharmacologists, chemists, and biochemists because of their broad therapeutic potential. In addition to their diverse biological activities, steroid derivatives have demonstrated significant antiparasitic properties, including promising antileishmanial activity.

The steroid compounds investigated by our research group are initially designed as potential anticancer agents. Taking into account their biological potential, a rational approach was to employ different disciplines to identify promising steroid-based compounds as safe and efficient antiparasitic agents. In the present study, a series of ten derivatives bearing different carbamate groups was subjected to in silico predictions of antileishmanial activity, relevant human protein targets, and toxicity profiling, using available online tools such as Way2Drug-Pass online, ADMETlab 2.0 and SwissADME. Only one compound showed the best properties both in terms of potential antileishmanial activity and in terms of safety and oral bioavailability.