Synthesis and Bio-evaluation of 7-trifluromethyl Substituted 4-aminoquinoline Derivatives as Antileishmanial Agents

Author(s): Shreekant Deshpande*, Rahul Shivahare, Utsab Debnath, Shraddha A. Sane, Suman Gupta, Seturam B Katti.

Journal Name: The Natural Products Journal

Volume 7 , Issue 2 , 2017

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Graphical Abstract:


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.

Keywords: 4-aminoquinoline, biological activity, hamster model, Leishmania donovani, luciferase assay, antileishmanial agents.

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Article Details

Year: 2017
Page: [137 - 143]
Pages: 7
DOI: 10.2174/2210315507666161206123513
Price: $58

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