Synthesis and antiplasmodial activity of new heteroaryl derivatives of 7-chloro-4-aminoquinoline
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Data di Pubblicazione:
2011
Citazione:
Synthesis and antiplasmodial activity of new heteroaryl derivatives of 7-chloro-4-aminoquinoline / M. Casagrande, A. Barteselli, N. Basilico, S. Parapini, D. Taramelli, A. Sparatore. ((Intervento presentato al 24. convegno Congresso Nazionale della Società Chimica Italiana tenutosi a Lecce nel 2011.
Abstract:
Presently, the most promising and successful strategy in fighting malaria is the
artemisinin-based combination therapy (ACT). Recent reports of ACT treatment
failure in southeast Asia and the potential emergence of artemisinin resistance
indicate that the search of new drugs or new combinations is still highly necessary.
In order to develop new classes of antimalarial agents, we recently demonstrated
that the replacement of the phenolic ring of amodiaquine and tebuquine with a
pyrrole nucleus, still linked to the quinoline moiety through the usual NH, is
associated with a good activity against both chloroquine sensitive (CQ-S) and
chloroquine-resistant (CQ-R) strains of P. falciparum [1-2].
With the aim to investigate the effect of other different heterocyclic rings linked to
the 4-aminoquinoline nucleus on the antimalarial activity, a set of 7-chloro-N-
(heteroaryl)-methyl-4-aminoquinoline and 7-chloro-N-(heteroaryl)-4-
aminoquinoline was synthesized and tested. All compounds exhibited from
moderate to high antiplasmodial activities, and the most potent molecules inhibited
the growth of both CQ-S and CQ-R strains of P. falciparum with IC50<30 nM. The
activity was strongly influenced both by the presence of a methylenic group, as a
spacer between the 4-aminoquinoline and the heterocyclic ring, and by the presence
of a basic head. Moreover, preliminary data indicate that the new compounds
exhibit low toxicity against a human endothelial cell line (HMEC-1). All these
results confirm that the presence of an heteroaryl moiety in the side chain of 7-
chloro-4-aminoquinoline is useful for the design and development of new powerful
antimalarial agents.
Tipologia IRIS:
14 - Intervento a convegno non pubblicato
Keywords:
Malaria ; 7-chloro-N-(heteroaryl)-methyl-4-aminoquinoline ; 7-chloro-N-(heteroaryl)-4-
aminoquinoline ; antimalarial agents
Elenco autori:
M. Casagrande, A. Barteselli, N. Basilico, S. Parapini, D. Taramelli, A. Sparatore
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