We report the design (in silico ADMET criteria), synthesis, cytotoxicity studies (HepG-2 cells), and biological evaluation of 15 hydrazine/hydrazide quinoxaline 1,4-di-N-oxide derivatives against the 3D7 chloroquine sensitive strain and FCR-3 multidrug resistant strain of Plasmodium falciparum and Leishmania infantum (axenic amastigotes). Fourteen of derivatives are novel quinoxaline 1,4-di-N-oxide derivatives. Compounds 18 (3D7 IC_{50}=1.40μM, FCR-3 IC_{50}=2.56μM) and 19 (3D7 IC_{50}=0.24μM, FCR-3 IC_{50}=2.8μM) were identified as the most active against P. falciparum, and they were the least cytotoxic (CC_{50}-values>241μM) and most selective (SI>86). None of the compounds tested against L. infantum were considered to be active. Additionally, the functional role of the hydrazine and hydrazide structures were studied in the quinoxaline 1,4-di-N-oxide system.
【저자키워드】 malaria, Leishmaniasis, hydrazide, Hydrazine, Quinoxaline 1,4-di-N-oxide.,