Amino acid, dipeptide and pseudodipeptide conjugates of ring-substituted 8-aminoquinolines: Synthesis and evaluation of anti-infective, β-haematin inhibition and cytotoxic activities

Three new series of 8-aminoquinolines with modifications in the side-chain by conjugation with amino acids, dipeptides and pseudodipeptides have been synthesized. The synthesized compounds were tested for in vitro antimalarial activity against chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum strains, in vitro cytotoxicity in mammalian kidney cells (Vero), in vitro antileishmanial activity against Leishmania donovani, in vitro antimicrobial activity and in vitro inhibition of β-haematin formation. The promising compounds were also evaluated for in vivo blood-schizontocidal antimalarial activity against Plasmodium berghei infected mice. The analogues 55 and 101 produced highest antimalarial activities, in vitro. Analogues 52 and 59 exhibited promising antileishmanial and broad spectrum of antifungal activities, respectively.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► New 8-aminoquinolines with modification in the side-chain have been synthesized. ► Analogues 55 and 101 are the most active antimalarials (IC50 = 0.13–0.63 μg/mL). ► Analogue 52 is a promising antileishmanial with IC50 and IC90 of 3.5 and 7 μg/mL, respectively. ► Analogue 59 exhibited best antifungal activities (IC50 = 3.55–11.16 μg/mL).