Background: Visceral Leishmaniasis (VL) is a fatal disseminated protozoan infection.
VL threatens 200 million people in 62 countries and responsible for 40,000 deaths each year. Chemotherapy
is the only tool for the treatment of VL, but, as yet, none of the available drugs are ideal
for treatment due to high toxicity, resistance issues and prohibitive prices. Hence, there is an urgent
need for the development of new and safer drugs.
Methods: In view of this, a series of 7-trifluoromethyl-4-aminoquinoline derivatives were synthesized
and evaluated for in vitro and in vivo antileishmanial activity against promastigote as well as
amastigote forms of Leishmania donovani.
Results: All the analogues displayed 81-99% inhibition of promastigotes at 10 μM concentration. Most
of the analogues exhibited good in vitro antiamastigote activity (IC50 = 5.3 - 9.6 μM) compared to reference
compounds, chloroquine (15.3 μM) and miltefosine (8.1 μM). The compounds exhibiting
antiamastigote activity in vitro were further tested for in vivo efficacy in Leishmania donovani/hamster
model. Amongst all, compound 6c showed 76.02 ± 13.60% inhibition of Leishmania parasite in treated
animals as compared to infected untreated hamsters on day 27 post infection.
Conclusion: The present results indicate the potential of aminoquinoline scaffold for further optimization.