Avaliação do potencial leishmanicida de derivados ftalimido-1,4naftoquinonas e ftalimido-1,2,3-triazolil-1,4-naftoquinonas

Abstract

Leishmaniasis are neglected parasitic diseases that affect millions of people, with poor treatment due mainly to toxicity and the ability to induce parasitic resistance. One of the key strategies for improving leishmaniasis therapy is the discovery of new drugs through chemical synthesis. The objective of this work was to investigate the in vitro leishmanicidal activity of unpublished 1,4-naphthoquinone derivatives. Cytotoxicity was evaluated in macrophages of lineage J774.A1 through the MTT colorimetric assay and leishmanicidal activity in L. amazonensis and L. chagasi promastigotes cultures by direct counting under an optical microscope. Statistical analyzes were performed in the GraphPad Prism program. All the derivatives showed leishmanicidal activity against L. chagasi, and only J4Br was not active against L. amazonensis. It was observed activity above 50% against L. amazonensis for J3Br (63.2 ± 8.2% with IC50 21.8 ± 4.1 μM), J4 (86.4 ± 5.5% with IC50 32.1 ± 15.5 μM), J6 (80.4 ± 7.5% with IC50 57.4 ± 6.9 μM), J6Br (85.0 ± 5.2% with IC50 63.6 ± 11.5 μM), J01.3 (100% with IC50 5,7 ± 0,8 μM), J02.3 (60.9 ± 13.0% with IC50 21.3 ± 16.3 µM) and J03.3 (80.4 ± 7.5% with IC50 8.6 ± 8.4 μM), and against L. chagasi for J3 (58.3 ± 6.8% with IC50 27.8 ± 1.1 μM), J4 (89.6 ± 4.1% with IC50 20.0 ± 4.8 μM), J6Br (58.3 ± 8.3% with IC50 89.5 ± 10.3 μM), J01.3 (100% with IC50 7.3 ± 0.5 μM) and J03.3 (89.5 ± 4.1% with IC50 8.1 ± 0.3 μM). Derivatives J3Br, J4Br and J02.3 showed no toxicity to macrophages, whereas J3 and J4 had toxicity below 50% and J6, J6Br, J01.3 and J03.3 above 50%. The derivatives have shown promising molecules for their leishmanicidal activity, however, aspects related to the toxicity of these substances still need to be improved.