Theoretical study of new LmDHODH and LmTXNPx complexes: structure-based relationships

In this work, a series of eight novel ring-substituted styrylquinolines were synthesized, and in silico physicochemical properties were estimated. The inhibitory activity of these compounds was evaluated in intracellular amastigotes of Leishmania (Viannia) panamensis, and their affinity for L. major dihydroorotate dehydrogenase DHODH (LmDHODH) and L. major tryparedoxin peroxidase TXNPx (LmTXNPx) was calculated by molecular docking, NCI index, and the recently developed IGM analysis, providing us useful insights about the forces governing the ligand-protein coupling. The eight synthesized molecules do not break the Lipinski, Ghose, Veber, Egan, and Muegge rules. Therefore, the bioavailability and absorption will not be poor. [Figure not available: see fulltext.]