In Vitro and In Silico Evaluations of the Antileishmanial Activities of New Benzimidazole-Triazole Derivatives

SIMPLE SUMMARY: Leishmaniasis is a protozoan disease seen in many vertebrates, caused by 20 different Leishmania species, and transmitted by the bite of flies, also known as vector sandflies. Leishmaniasis shows clinical changes such as subclinical, localized (cutaneous leishmaniasis), or widespread infection (cutaneous, mucosal, or visceral), depending on the parasite and host factors. Poor vector (sandfly) control, a lack of immunizations, restricted access to new and affordable medications, and ineffective drug research efforts are the current challenges to effective prevention and management. Drugs used in leishmaniasis chemotherapy may have nephrotoxic, hepatotoxic, and teratogenic side effects. Although many drug combinations have been developed for treatment, new drug formulations are needed due to the emergence of resistance. Some procedures need to be carried out to find new formulations. In this study, the synthesis of the new benzimidazole-triazole therapy, which is frequently used in the structure of drug molecules, is examined, and its antileishmanial activities are evaluated. ABSTRACT: Benzimidazole and triazole rings are important pharmacophores, known to exhibit various pharmacological activities in drug discovery. In this study, it was purposed to synthesize new benzimidazole-triazole derivatives and evaluate their antileishmanial activities. The targeted compounds (5a–5h) were obtained after five chemical reaction steps. The structures of the compounds were confirmed by spectral data. The possible in vitro antileishmanial activities of the synthesized compounds were evaluated against the Leishmania tropica strain. Further, molecular docking and dynamics were performed to identify the probable mechanism of activity of the test compounds. The findings revealed that compounds 5a, 5d, 5e, 5f, and 5h inhibited the growth of Leishmania tropica to various extents and had significant anti-leishmanial activities, even if some orders were higher than the reference drug Amphotericin B. On the other hand, compounds 5b, 5c, and 5g were found to be ineffective. Additionally, the results of in silico studies have presented the existence of some interactions between the compounds and the active site of sterol 14-alpha-demethylase, a biosynthetic enzyme that plays a critical role in the growth of the parasite. Therefore, it can be suggested that if the results obtained from this study are confirmed with in vivo findings, it may be possible to obtain some new anti-leishmanial drug candidates.