A Novel Series of [1,2,4]Triazolo[4,3-a]Pyridine Sulfonamides as Potential Antimalarial Agents: In Silico Studies, Synthesis and In Vitro Evaluation.

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Veronika R KarpinaLouis Maes

Abstract

For the development of new and potent antimalarial drugs, we designed the virtual library with three points of randomization of novel [1,2,4]triazolo[4,3-a]pyridines bearing a sulfonamide fragment. The library of 1561 compounds has been investigated by both virtual screening and molecular docking methods using falcipain-2 as a target enzyme. 25 chosen hits were synthesized and evaluated for their antimalarial activity in vitro against Plasmodium falciparum. 3-Ethyl-N-(3-fluorobenzyl)-N-(4-methoxyphenyl)-[1,2,4]triazolo[4,3-a]pyridine-6-sulfonamide and 2-(3-chlorobenzyl)-8-(piperidin-1-ylsulfonyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one showed in vitro good antimalarial activity with inhibitory concentration IC50 = 2.24 and 4.98 μM, respectively. This new series of compounds may serve as a starting point for future antimalarial drug discovery programs.

References

Apr 1, 1979·The Journal of Pharmacy and Pharmacology·D L WiseG J McCormick
Jun 1, 1993·The American Journal of Tropical Medicine and Hygiene·M T MaklerD J Hinrichs
Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
Jan 26, 2005·Journal of Chemical Information and Modeling·Gerhard Wolber, Thierry Langer
Oct 20, 2006·Journal of Computer-aided Molecular Design·Gerhard WolberThierry Langer
Sep 25, 2007·Bioorganic & Medicinal Chemistry·Luiz Everson da SilvaBoris Schmidt
Aug 1, 2008·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·S-F Zhou
Dec 2, 2008·Bioorganic & Medicinal Chemistry·Kekeli Ekoue-KoviChristian Wolf
Jun 16, 2009·Medicinal Research Reviews·Roberta EttariNicola Micale
Nov 17, 2009·Bioorganic & Medicinal Chemistry Letters·Derek C MartynJon Clardy
Apr 13, 2010·The Journal of Infectious Diseases·Colin J SutherlandSpencer D Polley
May 3, 2011·Bioorganic & Medicinal Chemistry Letters·Paul B McKayDarren Fayne
Apr 25, 2012·Journal of Tropical Medicine·Kailash C Pandey, Rajnikant Dixit
Feb 19, 2015·Pharmacology Research & Perspectives·Hilde LavreysenAnton Megens
Dec 26, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Teresa KasererDaniela Schuster
Oct 25, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ifedayo Victor Ogungbe, William N Setzer
May 15, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Sahil KumarRajesh K Singh
Oct 16, 2018·Chemical Biology & Drug Design·Kamila Anna MeissnerCarsten Wrenger

Methods Mentioned

BETA
in silico methods
NMR
column chromatography
FCS

Related Concepts

pyridine sulfonamide
Antimalarials
Binding Sites
Cultured Cell Line
In Silico
Medicinal Plants Testing, Preclinical
Homo sapiens
Ligands
Plasmodium falciparum
Pyridines

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.

Related Papers

British Journal of Pharmacology
W H Richards, S G Williams
British Medical Journal
Concours médical
F DAUCHY
Produits pharmaceutiques
O S VAN
© 2021 Meta ULC. All rights reserved