New hydrazine and hydrazide quinoxaline 1,4-di-N-oxide derivatives: In silico ADMET, antiplasmodial and antileishmanial activity

Miguel Quiliano; Adriana Pabón; Gustavo Ramirez-Calderon; Carlos Barea; Eric Deharo; Silvia Galiano; Ignacio Aldana

doi:10.1016/j.bmcl.2017.02.049

New hydrazine and hydrazide quinoxaline 1,4-di-N-oxide derivatives: In silico ADMET, antiplasmodial and antileishmanial activity

Miguel Quiliano
, Adriana Pabón
, Gustavo Ramirez-Calderon
, Carlos Barea
, Eric Deharo
, Silvia Galiano
, Ignacio Aldana

Universidad de Navarra
Universidad de Antioquia
Université Paul Sabatier Toulouse III

Research output: Contribution to journal › Article › peer-review

41 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	1820-1825
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	27
Issue number	8
DOIs	https://doi.org/10.1016/j.bmcl.2017.02.049
State	Published - 2017
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Hydrazide
Hydrazine
Leishmaniasis
Malaria
Quinoxaline 1,4-di-N-oxide

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10.1016/j.bmcl.2017.02.049

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title = "New hydrazine and hydrazide quinoxaline 1,4-di-N-oxide derivatives: In silico ADMET, antiplasmodial and antileishmanial activity",

abstract = "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.",

keywords = "Hydrazide, Hydrazine, Leishmaniasis, Malaria, Quinoxaline 1,4-di-N-oxide",

author = "Miguel Quiliano and Adriana Pab{\'o}n and Gustavo Ramirez-Calderon and Carlos Barea and Eric Deharo and Silvia Galiano and Ignacio Aldana",

note = "Publisher Copyright: {\textcopyright} 2017 Elsevier Ltd",

year = "2017",

doi = "10.1016/j.bmcl.2017.02.049",

language = "Ingl{\'e}s",

volume = "27",

pages = "1820--1825",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

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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

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 -

New hydrazine and hydrazide quinoxaline 1,4-di-N-oxide derivatives: In silico ADMET, antiplasmodial and antileishmanial activity

Abstract

UN SDGs

Keywords

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