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
Veronika R. Karpina,
Svitlana S. Kovalenko,
Sergiy M. Kovalenko,
Oleksandr G. Drushlyak,
Natalya D. Bunyatyan,
Victoriya A. Georgiyants,
Vladimir V. Ivanov,
Thierry Langer,
Louis Maes
Affiliations
Veronika R. Karpina
Department of Pharmaceutical Chemistry, National University of Pharmacy, 53 Pushkinska str., 61002 Kharkiv, Ukraine
Svitlana S. Kovalenko
Department of Pharmaceutical Chemistry, National University of Pharmacy, 53 Pushkinska str., 61002 Kharkiv, Ukraine
Sergiy M. Kovalenko
Department of Organic Chemistry, V.N. Karazin Kharkiv National University, 4 Svobody Sq., 61022 Kharkiv, Ukraine
Oleksandr G. Drushlyak
Department of Pharmaceutical Chemistry, National University of Pharmacy, 53 Pushkinska str., 61002 Kharkiv, Ukraine
Natalya D. Bunyatyan
Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 8-2 Trubetskaya str., Moscow 119991, Russia
Victoriya A. Georgiyants
Department of Pharmaceutical Chemistry, National University of Pharmacy, 53 Pushkinska str., 61002 Kharkiv, Ukraine
Vladimir V. Ivanov
Department of Organic Chemistry, V.N. Karazin Kharkiv National University, 4 Svobody Sq., 61022 Kharkiv, Ukraine
Thierry Langer
Department of Pharmaceutical Chemistry, University of Vienna, Althanstraße 14, A-1090 Vienna, Austria
Louis Maes
Laboratory of Microbiology, Parasitology and Hygiene, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium
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.
