Synthesis and structure-activity relationship of 3-phenylquinoxaline 1,4-di-N-oxide derivatives as antimalarial agents

European Journal of Medicinal Chemistry
Esther VicenteAntonio Monge

Abstract

As a continuation of our research and with the aim of obtaining new antimalarial agents, new series of 3-phenylquinoxaline 1,4-di-N-oxide derivatives have been synthesized following the classical Beirut reaction. Antiplasmodial activity was evaluated in vitro against Plasmodium falciparum by the incorporation of [3H]-hypoxanthine. Cytotoxicity was tested in KB cells by AlamarBlue assay. Twenty-one of the 60 compounds that were assayed against 3D7 (CQ-sensitive) showed enough activity to be also evaluated against K1 (CQ-resistant) strain. Ten of them were shown to be more active than chloroquine in the resistant strain. The most interesting compounds are 7-(methyl or methoxy)-3-(4'-fluoro or chloro)phenylquinoxaline-2-carbonitrile 1,4-di-N-oxides because of their low IC50 and their high SI shown for the K1 strain, making them valid new leads.

Citations

Sep 29, 2011·Antimicrobial Agents and Chemotherapy·Edwin KamauJon Boyle
Feb 21, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ana GilIgnacio Aldana
Apr 24, 2013·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Carlos BareaIgnacio Aldana
May 25, 2010·Chemical Biology & Drug Design·Esther VicenteEduardo A Castro
May 8, 2014·ACS Combinatorial Science·Jhonny AzuajeEddy Sotelo
Aug 9, 2012·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Carlos BareaIgnacio Aldana
Aug 15, 2012·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yunzhen HuRong Sheng
Sep 20, 2019·International Journal of Molecular Sciences·Aušra Nemeikaitė-ČėnienėNarimantas Čėnas
May 7, 2020·International Journal of Molecular Sciences·Mindaugas LesanavičiusNarimantas Čėnas
Mar 24, 2020·Expert Opinion on Drug Discovery·Charu UpadhyayBrijesh Rathi
Dec 18, 2009·Journal of Medicinal Chemistry·Françoise NepveuJean-Pierre Nallet
Dec 7, 2010·Bioorganic & Medicinal Chemistry·Cátia RamalheteMaria-José U Ferreira

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antimalarial Agents (ASM)

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.

Antimalarial Agents

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.