TY - JOUR
T1 - New hydrazine and hydrazide quinoxaline 1,4-di-N-oxide derivatives
T2 - In silico ADMET, antiplasmodial and antileishmanial activity
AU - Quiliano, Miguel
AU - Pabón, Adriana
AU - Ramirez-Calderon, Gustavo
AU - Barea, Carlos
AU - Deharo, Eric
AU - Galiano, Silvia
AU - Aldana, Ignacio
N1 - Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2017
Y1 - 2017
N2 - 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 IC50 = 1.40 μM, FCR-3 IC50 = 2.56 μM) and 19 (3D7 IC50 = 0.24 μM, FCR-3 IC50 = 2.8 μM) were identified as the most active against P. falciparum, and they were the least cytotoxic (CC50-values > 241 μM) 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.
AB - 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 IC50 = 1.40 μM, FCR-3 IC50 = 2.56 μM) and 19 (3D7 IC50 = 0.24 μM, FCR-3 IC50 = 2.8 μM) were identified as the most active against P. falciparum, and they were the least cytotoxic (CC50-values > 241 μM) 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.
KW - Hydrazide
KW - Hydrazine
KW - Leishmaniasis
KW - Malaria
KW - Quinoxaline 1,4-di-N-oxide
UR - https://www.scopus.com/pages/publications/85014857060
U2 - 10.1016/j.bmcl.2017.02.049
DO - 10.1016/j.bmcl.2017.02.049
M3 - Artículo
C2 - 28291694
AN - SCOPUS:85014857060
SN - 0960-894X
VL - 27
SP - 1820
EP - 1825
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 8
ER -
