Synthesis and antiplasmodial activity of 1,2,3-triazole-naphthoquinone conjugates

Sandra Oramas-Royo, Priscila López-Rojas, Ángel Amesty, David Gutiérrez, Ninoska Flores, Patricia Martín-Rodríguez, Leandro Fernández-Pérez, Ana Estévez-Braun

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8 Scopus citations

Abstract

A series of 34 1,2,3-triazole-naphthoquinone conjugates were synthesized via copper-catalyzed cycloaddition (CuAAC). They were evaluated for their in vitro antimalarial activity against chloroquine-sensitive strains of Plasmodium falciparum and against three different tumor cell lines (SKBr-3, MCF-7, HEL). The most active antimalarial compounds showed a low antiproliferative activity. Simplified analogues were also obtained and some structure–activity relationships were outlined. The best activity was obtained by compounds 3s and 3j, having IC50 of 0.8 and 1.2 μM, respectively. Molecular dockings were also carried on Plasmodium falciparum enzyme dihydroorotate dehydrogenase (PfDHODH) in order to rationalize the results.

Original languageEnglish
Article number3917
JournalMolecules
Volume24
Issue number21
DOIs
StatePublished - 2019

Bibliographical note

Funding Information:
Author Contributions: D.G. and N.F., antiplasmodial activity; P.M.-R. and L.F.-P., antiproliferative activity; A.A., computational studies; P.L.-R. and S.O.-R., synthesis, purification, and characterization of all compounds; A.E.-B., conception, design, discussion of the results, drafting, and financial support of the manuscript submitted. All authors read and approved the final manuscript for submission to Molecules.

Funding Information:
Funding: We gratefully acknowledge the financial support from the Spanish Ministerio de Economía y Competitividad (MINECO) SAF 2015-65113-C2-1-R to A.E.B. and SAF 2015-65113-C2-2-R to L.F.-P., Agencia Canaria de Investigación, Innovación y Sociedad de la Información (Pro ID 2017010071), Ministerio de Ciencias, Innovación y Universidades (MICINN (RTI2018-094356-B-C21). These projects are also co-funded by the European Regional Development Fund (FEDER).

Funding Information:
We gratefully acknowledge the financial support from the Spanish Ministerio de Econom?a y Competitividad (MINECO) SAF 2015-65113-C2-1-R to A.E.B. and SAF 2015-65113-C2-2-R to L.F.-P., Agencia Canaria de Investigaci?n, Innovaci?n y Sociedad de la Informaci?n (Pro ID 2017010071), Ministerio de Ciencias, Innovaci?n y Universidades (MICINN (RTI2018-094356-B-C21). These projects are also co-funded by the European Regional Development Fund (FEDER). P.L.R. thanks the Spanish MINECO for a pre-doctoral grant (FPU-Program). A.A. and S.O.R. thank the Cabildo de Tenerife (Agust?n de Betancourt Program).

Publisher Copyright:
© 2019 by the authors.

Keywords

  • 1,2,3-triazole-naphthoquinones
  • Copper-catalyzed cycloaddition
  • Docking
  • Malaria
  • Plasmodium falciparum

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