Synthesis and antileishmanial activity of naphthoquinone-based hybrids

SUMMARY Introduction: Leishmaniasis is a disease caused by protozoa of the genus Leishmania and is considered endemic in 98 countries. Treatment with pentavalent antimonials has a high toxicity, which motivates the search for effective and less toxic drugs. α- and β-lapachones have shown different biological activities, including antiprotozoa. In recent studies, the isonicotinoylhydrazone and phthalazinylhydrazone groups were considered innovative in the development of antileishmania drugs. Molecular hybridization is a strategy for the rational development of new prototypes, where the main compound is produced through the appropriate binding of pharmacophoric subunits. Aims: To synthesize four hybrids of α- and β-lapachones, together with the isonicotinoylhydrazone and phthalazinylhydrazone groups and to determine the antileishmania activity against the promastigotic forms of L. amazonensis, L. infantum and L. major. Results: β-lapachone derivatives were more active against all tested leishmania species. βACIL (IC50 0.044μM) and βHDZ (IC50 0.023μM) showed 15-fold higher activity than amphotericin B. The high selectivity index exhibited by the compounds indicates greater safety for vertebrate host cells. Conclusion: The results of this work show that the hybrids βACIL and (3HDZ are promising molecules for the development of new antileishmania drugs.

Bibliographic Details

Main Authors:	Guimarães,Délis Galvão, Simplício,Sidney Silva, Sousa,Valéria Carlos de, Rodrigues,Klinger Antonio da Franca, Carvalho,Fernando Aércio A., Carneiro,Sabrina M. P., Costa,Marcília Pinheiro da, Gonsalves,Arlan de A., Araújo,Cleônia Roberta M.
Format:	Digital revista
Language:	English
Published:	Departamento de Farmácia, Facultad de Ciencias, Universidade Nacional da Colombia 2021
Online Access:	http://www.scielo.org.co/scielo.php?script=sci_arttext&pid=S0034-74182021000200505
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