Resumen

LEON, Caritza et al. Síntesis y Actividad Antimalárica de Derivados 3-Cloro- 2N-Aminosustituido-1,4-Naftoquinona. Revista de Investigación [online]. 2008, vol.32, n.64, pp.189-209. ISSN 1010-2914.

We described the synthesis of 3-chloro-2N-[1’-alkyl-1’-(4”- chlorophenylcarbamoyl) methyl]amine-1,4-naphthoquinones derivatives. The new compounds were characterized through IR, ¹H NMR, ¹³C NMR and Mass Spectrometry. The biological evaluation of these derivatives was carry out by inhibition of beta-hematin formation in vitro and the inhibition of cultured P. falciparum parasites. The most active compound resulted the 3-chloro-2N-[1’-methyl-1’-(4”-chlorophenylcarbamoyl) methyl] amine-1,4-naphthoquinone 15, Cl₅₀ 1.92 μM, as an inhibitor in cultured P. falciparum parasites, while compound 3-chloro-2N-[1’-(phenylmethyl)- 1’-(4”-chlorophenylcarbamoyl) methyl]amine-1,4-naphthoquinone 17 was the best as inhibitor of beta-hematin formation with an Cl₅₀ of 6.07 mM. These studies open up the novel possibility of development of 3-chloro-2Naminesubstituted- 1,4-naftoquinonas derivatives as potentials antimalarials that target beta-hematin formation and the inhibition of the development of cultured P. falciparum parasites, which should help delay the rapid onset of resistance to drugs acting at only a single site. These compounds represent a new family of promising antimalarials.

Palabras clave : Antimalarial; naphthoquinones; amino acids; hemozoin.