A new series of amodiaquine analogues modified in the basic side chain with in vitro antileishmanial and antiplasmodial activity


Guglielmo, S; Bertinaria, M; Rolando, B; Crosetti, M; Fruttero, R; Yardley, V; Croft, SL; Gasco, A; (2009) A new series of amodiaquine analogues modified in the basic side chain with in vitro antileishmanial and antiplasmodial activity. European journal of medicinal chemistry, 44 (12). pp. 5071-5079. ISSN 0223-5234 DOI: https://doi.org/10.1016/j.ejmech.2009.09.012

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Abstract

The synthesis and the study of new amodiaquine derivatives bearing modified lateral basic chains as new agents with both antimalarial and antileishmanial activities are reported. The compounds were tested in vitro against Leishmania donovani MHOM/ET/67/HU3 and 2 strains of Plasmodium falciparum, 3D7 and K1. All the compounds show complex ionisation profiles. At physiological pH the ionised form(s) are in equilibrium with the uncharged form, while at acid pH all the products exist largely as protonated forms. The antiprotozoal profile indicates that all derivatives are endowed with both antimalarial and antileishmanial activity. Interestingly amodiaquine, together with some synthesised derivatives (11, 12, 15, 27, 34), displayed antileishmanial activity in the low micromolar range, although these compounds were also cytotoxic and have a narrow therapeutic window, most of the synthesised compounds proved to be potent antimalarials, a few of them showing a good activity against the chloroquine resistant K1 strain. (C) 2009 Elsevier Masson SAS. All rights reserved.

Item Type: Article
Keywords: Amodiaquine analogues, Leishmania donovani, Plasmodium falciparum, Antiprotozoals, derivatives, antimalarial, cytotoxicity, invitro
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: Leishmaniasis Group
Malaria Centre
Neglected Tropical Diseases Network
PubMed ID: 19811859
Web of Science ID: 272928600033
URI: http://researchonline.lshtm.ac.uk/id/eprint/4308

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