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

共 50 条

[31] Novel [1,2,4] Triazol [4,3-a] Pyridine Derivatives as Potential Selective c-Met Inhibitors with Improved Pharmacokinetic Properties
Zhao, Junjun
Gou, Shaohua
Zhang, Xiaobing
Liang, Yan
Fang, Lei
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, 2017, 17 (08) : 1102 - 1112
[32] Synthesis and antitumor activity of novel pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5-one derivatives
El-Nassan, Hala B.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2011, 46 (06) : 2031 - 2036
[33] Synthesis and biological evaluation of novel 6-alkoxy-3-aryl-[1,2,4]triazolo[4,3-b][1,2,4,5] tetrazines
Shi, Run-Jie
Yang, Zhen-Zhen
Gaol, Ye-Tao
Cai, Wen-Jin
Ye, Can
Xu, Feng
Wang, John
JOURNAL OF CHEMICAL RESEARCH, 2019, 43 (9-10) : 313 - 318
[34] Synthesis, antitumor evaluation and 3D-QSAR studies of [1,2,4]triazolo[4,3-b][1,2,4,5] tetrazine derivatives
Xu, Feng
Yang, Zhen-zhen
Ke, Zhong-lu
Xi, Li-min
Yan, Qi-dong
Yang, Wei-qiang
Zhu, Li-qing
Lin, Fei-lei
Lv, Wei-ke
Wu, Han-gui
Wang, John
Li, Hai-bo
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2016, 26 (19) : 4580 - 4586
[35] Synthesis of Oxazolo[5,4-d][1,2,4]triazolo[4,3-a]pyrimidines as a New Class of Heterocyclic Compounds
Akbarzadeh, Marzieh
Bakavoli, Mehdi
Eshghi, Hossein
Shiri, Ali
JOURNAL OF HETEROCYCLIC CHEMISTRY, 2016, 53 (03) : 832 - 839
[36] Pyrazolo[4,3-c]pyridine Sulfonamides as Carbonic Anhydrase Inhibitors: Synthesis, Biological and In Silico Studies
Angeli, Andrea
Kartsev, Victor
Petrou, Anthi
Lichitsky, Boris
Komogortsev, Andrey
Pinteala, Mariana
Geronikaki, Athina
Supuran, Claudiu T.
PHARMACEUTICALS, 2022, 15 (03)
[37] 1,1′-Carbonyldiimidazole (CDI) Mediated Coupling and Cyclization To Generate [1,2,4]Triazolo[4,3-a]pyridines
Baucom, Kyle D.
Jones, Sian C.
Roberts, Scott W.
ORGANIC LETTERS, 2016, 18 (03) : 560 - 563
[38] Synthesis of [1,2,4]Triazolo[4,3-a]piperazin-6-ones: An Approach to the Triazole-Fused Ketopiperazine Scaffold
Salah, Khoubaib Ben Haj
Legrand, Baptiste
Bibian, Mathieu
Wenger, Emmanuel
Fehrentz, Jean-Alain
Denoyelle, Severine
ORGANIC LETTERS, 2018, 20 (11) : 3250 - 3254
[39] Differentiation between [1,2,4]triazolo[1,5-a]pyrimidine and [1,2,4]triazolo[4,3-a]pyrimidine regioisomers by 1H-15N HMBC experiments
Salgado, Antonio
Varela, Carmen
Garcia Collazo, Ana Maria
Pevarello, Paolo
MAGNETIC RESONANCE IN CHEMISTRY, 2010, 48 (08) : 614 - 622
[40] Pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine Sulfonamides as an Important Scaffold for Anticancer Drug Discovery-In Vitro and In Silico Evaluation
Kciuk, Mateusz
Marciniak, Beata
Celik, Ismail
Zerroug, Enfale
Dubey, Amit
Sundaraj, Rajamanikandan
Mujwar, Somdutt
Bukowski, Karol
Mojzych, Mariusz
Kontek, Renata
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2023, 24 (13)

← 1 2 3 4 5 →