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

被引：14

作者：

Karpina, Veronika R. ^{[1
]}

Kovalenko, Svitlana S. ^{[1
]}

Kovalenko, Sergiy M. ^{[2
,3
]}

Drushlyak, Oleksandr G. ^{[1
]}

Bunyatyan, Natalya D. ^{[3
,4
]}

Georgiyants, Victoriya A. ^{[1
]}

Ivanov, Vladimir V. ^{[2
]}

Langer, Thierry ^{[5
]}

Maes, Louis ^{[6
]}

机构：

[1] Natl Univ Pharm, Dept Pharmaceut Chem, 53 Pushkinska Str, UA-61002 Kharkiv, Ukraine

[2] Kharkov Natl Univ, Dept Organ Chem, 4 Svobody Sq, UA-61022 Kharkiv, Ukraine

[3] IM Sechenov First Moscow State Med Univ, Fed State Autonomous Educ Inst Higher Educ, Minist Hlth Russian Federat, Sechenov Univ, 8-2 Trubetskaya Str, Moscow 119991, Russia

[4] Minist Hlth Russian Federat, Fed State Budgetary Inst Sci Ctr Expert Evaluat M, Petrovsky Blvd 8,Bld 2, Moscow 127051, Russia

[5] Univ Vienna, Dept Pharmaceut Chem, Althanstr 14, A-1090 Vienna, Austria

[6] Univ Antwerp, Lab Microbiol Parasitol & Hyg, Univ Pl 1, B-2610 Antwerp, Belgium

来源：

MOLECULES | 2020年 / 25卷 / 19期

关键词：

1; 2; 4]triazolo[4; 3-a]pyridines; sulfonamide; Plasmodium falciparum; antimalarial; falcipain-2; virtual screening; molecular docking; PLASMODIUM-FALCIPARUM; CYSTEINE PROTEASE; INHIBITORS; IDENTIFICATION; PHARMACOPHORE; DEHYDROGENASE; DOCKING;

D O I：

10.3390/molecules25194485

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 mu M, respectively. This new series of compounds may serve as a starting point for future antimalarial drug discovery programs.

引用

页数：33

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