Arch Venez Med Trop

Abstract

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.