Trypanocidal properties, structure-activity relationship and computational studies of quinoxaline 1,4-di-N-oxide derivatives

Yannick Estevez, Miguel Quiliano, Asunción Burguete, Billy Cabanillas, Mirko Zimic, Edith Málaga, Manuela Verástegui, Silvia Pérez-Silanes, Ignacio Aldana, Antonio Monge, Denis Castillo, Eric Deharo

Research output: Contribution to journalArticle

Abstract

Pyrazole and propenone quinoxaline derivatives were tested against intracellular forms of Leishmania peruviana and Trypanosoma cruzi. Both series were tested for toxicity against proliferative and non-proliferative cells. The pyrazole quinoxaline series was quite inactive against T. cruzi; however, the compound 2,6-dimethyl-3-f-quinoxaline 1,4-dioxide was found to inhibit 50% of Leishmania growth at 8.9. μM, with no impact against proliferative kidney cells and with low toxicity against THP-1 cells and murine macrophages. The compounds belonging to the propenone quinoxaline series were moderately active against T. cruzi. Among these compounds, two were particularly interesting, (2E)-1-(7-fluoro-3-methyl-quinoxalin-2-yl)-3-(3,4,5-trimethoxy-phenyl)-propenone and (2E)-3-(3,4,5-trimethoxy-phenyl)-1-(3,6,7-trimethyl-quinoxalin-2-yl)-propenone. The former possessed selective activity against proliferative cells (cancer and parasites) and was inactive against murine peritoneal macrophages; the latter was active against Leishmania and inactive against the other tested cells. Furthermore, in silico studies showed that both series respected Lipinski's rules and that they confirmed a linear correlation between trypanocidal activities and Log. P. Docking studies revealed that compounds of the second series could interact with the poly (ADP-ribose) polymerase protein of Trypanosoma cruzi.

Original languageEnglish (US)
Pages (from-to)745-751
Number of pages7
JournalExperimental Parasitology
Volume127
Issue number4
DOIs
StatePublished - Apr 2011
Externally publishedYes

Fingerprint

Quinoxalines
Structure-Activity Relationship
Oxides
Trypanosoma cruzi
Leishmania
Poly(ADP-ribose) Polymerases
Peritoneal Macrophages
Computer Simulation
Parasites
Macrophages
Kidney
Growth
Neoplasms
Proteins

Keywords

  • Leishmania peruviana
  • Quinoxaline 1,4-di-N-oxide derivatives
  • Trypanosoma cruzi

ASJC Scopus subject areas

  • Parasitology
  • Immunology

Cite this

Trypanocidal properties, structure-activity relationship and computational studies of quinoxaline 1,4-di-N-oxide derivatives. / Estevez, Yannick; Quiliano, Miguel; Burguete, Asunción; Cabanillas, Billy; Zimic, Mirko; Málaga, Edith; Verástegui, Manuela; Pérez-Silanes, Silvia; Aldana, Ignacio; Monge, Antonio; Castillo, Denis; Deharo, Eric.

In: Experimental Parasitology, Vol. 127, No. 4, 04.2011, p. 745-751.

Research output: Contribution to journalArticle

Estevez, Y, Quiliano, M, Burguete, A, Cabanillas, B, Zimic, M, Málaga, E, Verástegui, M, Pérez-Silanes, S, Aldana, I, Monge, A, Castillo, D & Deharo, E 2011, 'Trypanocidal properties, structure-activity relationship and computational studies of quinoxaline 1,4-di-N-oxide derivatives', Experimental Parasitology, vol. 127, no. 4, pp. 745-751. https://doi.org/10.1016/j.exppara.2011.01.009
Estevez, Yannick ; Quiliano, Miguel ; Burguete, Asunción ; Cabanillas, Billy ; Zimic, Mirko ; Málaga, Edith ; Verástegui, Manuela ; Pérez-Silanes, Silvia ; Aldana, Ignacio ; Monge, Antonio ; Castillo, Denis ; Deharo, Eric. / Trypanocidal properties, structure-activity relationship and computational studies of quinoxaline 1,4-di-N-oxide derivatives. In: Experimental Parasitology. 2011 ; Vol. 127, No. 4. pp. 745-751.
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AU - Cabanillas, Billy

AU - Zimic, Mirko

AU - Málaga, Edith

AU - Verástegui, Manuela

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AU - Castillo, Denis

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