Synthesis and antileishmanial activity of naphthoquinone-based hybrids

• Published in: Revista colombiana de ciencias químico-farmacéuticas 2021, Vol.50 (2)
• Main Authors: Araújo, Cleônia Roberta Melo, Galvão Guimarães, Délis, Silva Simplício, Sidney, Carlos de Sousa, Valéria, Da Franca Rodrigues, Klinger Antonio, Aércio A. Carvalho, Fernando, M. P. Carneiro, Sabrina, Pinheiro da Costa, Marcília, De A. Gonsalves, Arlan
• Format: Article
• Language: English
• Subjects: Antiparasitic agents; Biological effects; Chemical synthesis; Composting; Drugs; Parasitic diseases; Protozoa; Toxic diseases; Vertebrates
• ISSN: 0034-7418; 1909-6356
• DOI: 10.15446/rcciquifa.v50n2.92861

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 βHDZ are promising molecules for the development of new antileishmania drugs.