%0 Journal Article
%9 ACL : Articles dans des revues avec comité de lecture répertoriées par l'AERES
%A Estevez, Y.
%A Quiliano, M.
%A Burguete, A.
%A Cabanillas, B.
%A Zimic, M.
%A Malaga, E.
%A Verastegui, M.
%A Perez-Silanes, S.
%A Aldana, I.
%A Monge, A.
%A Castillo, D.
%A Deharo, Eric
%T Trypanocidal properties, structure-activity relationship and computational studies of quinoxaline 1,4-di-N-oxide derivatives
%D 2011
%L fdi:010053425
%G ENG
%J Experimental Parasitology
%@ 0014-4894
%K Quinoxaline 1,4-di-N-oxide derivatives ; Leishmania peruviana ; Trypanosoma cruzi
%M ISI:000288592400004
%N 4
%P 745-751
%R 10.1016/j.exppara.2011.01.009
%U https://www.documentation.ird.fr/hor/fdi:010053425
%> https://www.documentation.ird.fr/intranet/publi/2011/04/010053425.pdf
%V 127
%W Horizon (IRD)
%X 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 mu M, 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)-p ropenone and (2E)-3-(3,4,5-trimethoxy-phenyl)-1-(3,6,7-trimethyl-quinoxalin-2-yl)-pro penone. 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 LogP. Docking studies revealed that compounds of the second series could interact with the poly (ADP-ribose) polymerase protein of Trypanosoma cruzi.
%$ 052