Docking analyses of aryltetralin lignans on Leishmania enzyme-based drug targets
Leishmaniasis is a parasitic disease caused by protozoa of the genus Leishmania. Worldwide it is calculated that 12 million people are currently infected and each year there are ca 2 million infections, it being furthermore estimated that 350 million people in 88 countries are at risk of being infected. Therefore, as part of our research on antileishmanial agents, in vitro leishmanicidal effects of five lignans, a diterpene, and a dihydrochalcone obtained from Pleurothyrium cinereum were evaluated on promastigotes of Leishmania panamensis and L. braziliensis. All compounds showed activity against Leishmania parasites at different levels. Dihydrochalcone was found to be the most potent antileishmanial compound on both parasites, whilst alryltetralyn (+)-otobaphenol, was found to be the most selective compound on L. panamensis. In order to observe a structure-activity relationship, Autodock Vina was used to dock the most stable conformers from optimized structures at DFT level of test compounds within the active site of three enzyme-based drug targets of Leishmania such as cysteine synthase, N-myristoyltransferase, and UDP-glucose pyrophosphorylase. Good correlations were found between in vitro activities and docking. Most stable conformer of (+)-otobaphenol was found to exhibit the best correlation. Aryltetralin lignans might be considered as good candidates for structural optimization leading antileishmanial agents.