Structure-activity relationships and mechanistic studies of novel mitochondria-targeted, leishmanicidal derivatives of the 4-aminostyrylquinoline scaffold

摘要

A new class of quinoline derivatives, bearing amino chains at C-4 and a styryl group at C-2, were tested on Leishmania donovani promastigotes and axenic and intracellular Leishmania pifanoi amastigotes. The introduction of the C-4 substituent improves the activity, which is due to interference with the mitochondrial activity of the parasite and its concomitant bioenergetic collapse by ATP exhaustion. Some compounds show a promising antileishmanial profile, with low micromolar or submicromolar activity on promastigote and amastigote forms and a good selectivity index. (C) 2019 Elsevier Masson SAS. All rights reserved.