Identification of protein kinase fibroblast growth factor receptor 1 (FGFR1) inhibitors among the derivatives of 5-(5,6-dimethoxybenzimidazol-1-yl)-3-hydroxythiophene-2-carboxylic acid

Volynets, Galyna P.; Lukashov, S. S.; Borysenko, I. P.; Gryshchenko, Andrii; Starosyla, Sergiy A.; Bdzhola, Volodymyr G.; Рубан, Т. А.; Iatsyshyna, A. P.; Лукаш, Л. Л.; Bilokin, Yaroslav V.; Yarmoluk, S. M.

doi:10.1007/s00706-019-02493-5

Cited by 5 publications

(5 citation statements)

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“…Compound cytotoxicity was determined by standard MTT assay 37 using human embryonic kidney 293 (HEK293) and human hepatocellular carcinoma (HepG2) cell lines according to the method described previously 38 . HEK 293 cell line was obtained from the Russian Cell Culture Collection (Institute of Cytology of the Russian Academy of Science, St.Petersburg, Russia) and HepG2 – from the Bank of Cell Lines from human and animal tissue (R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv, Ukraine).…”

Section: Methodsmentioning

confidence: 99%

Discovery of novel antituberculosis agents among 3-phenyl-5-(1-phenyl-1H-[1,2,3]triazol-4-yl)-[1,2,4]oxadiazole derivatives targeting aminoacyl-tRNA synthetases

Rybak

Balanda

Yatsyshyna

et al. 2021

Sci Rep

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Antibiotic resistance is a major problem of tuberculosis treatment. This provides the stimulus for the search of novel molecular targets and approaches to reduce or forestall resistance emergence in Mycobacterium tuberculosis. Earlier, we discovered a novel small-molecular inhibitor among 3-phenyl-5-(1-phenyl-1H-[1,2,3]triazol-4-yl)-[1,2,4]oxadiazoles targeting simultaneously two enzymes—mycobacterial leucyl-tRNA synthetase (LeuRS) and methionyl-tRNA synthetase (MetRS), which are promising molecular targets for antibiotic development. Unfortunately, the identified inhibitor does not reveal antibacterial activity toward M. tuberculosis. This study aims to develop novel aminoacyl-tRNA synthetase inhibitors among this chemical class with antibacterial activity toward resistant strains of M. tuberculosis. We performed molecular docking of the library of 3-phenyl-5-(1-phenyl-1H-[1,2,3]triazol-4-yl)-[1,2,4]oxadiazole derivatives and selected 41 compounds for investigation of their inhibitory activity toward MetRS and LeuRS in aminoacylation assay and antibacterial activity toward M. tuberculosis strains using microdilution assay. In vitro screening resulted in 10 compounds active against MetRS and 3 compounds active against LeuRS. Structure-related relationships (SAR) were established. The antibacterial screening revealed 4 compounds active toward M. tuberculosis mono-resistant strains in the range of concentrations 2–20 mg/L. Among these compounds, only one compound 27 has significant enzyme inhibitory activity toward mycobacterial MetRS (IC50 = 148.5 µM). The MIC for this compound toward M. tuberculosis H37Rv strain is 12.5 µM. This compound is not cytotoxic to human HEK293 and HepG2 cell lines. Therefore, 3-phenyl-5-(1-phenyl-1H-[1,2,3]triazol-4-yl)-[1,2,4]oxadiazole derivatives can be used for further chemical optimization and biological research to find non-toxic antituberculosis agents with a novel mechanism of action.

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Section: Methodsmentioning

confidence: 99%

Discovery of novel antituberculosis agents among 3-phenyl-5-(1-phenyl-1H-[1,2,3]triazol-4-yl)-[1,2,4]oxadiazole derivatives targeting aminoacyl-tRNA synthetases

Rybak

Balanda

Yatsyshyna

et al. 2021

Sci Rep

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“…3 Substituted 3hydroxythiophene partial structures can be dissected from drugs such as protiofate, oliceridine (Figure 1), arzoxifene, and LSZ102 (preclinical, Ph1), and other bioactive compounds. As additional examples, 3-hydroxythiophenes have been developed as inhibitors of protein tyrosine phosphatase 1B (diabetes type 2 treatment), 4 protein kinase fibroblast growth factor receptor 1 (anticancer), 5 17-hydroxysteroid dehydrogenase type 2 (osteoporosis treatment), 6 and 5-LOX/COX (inflammation treatment). 7 Carbene-platinum complexes with 3-hydroxythiophene-derived ligands proved to have significant antitumor activities, 8 while other derivatives display antiplasmodium 9 and antituberculosis activities.…”

Section: Coomementioning

confidence: 99%

“…Noncondensed substituted 3-hydroxythiophenes can be prepared by the formation of one, two, or three bonds from suitable starting materials by cyclizative condensations, alkylationcyclocondensations, or functionalization of an existing thiophene ring. [4][5][6]21,22 Substituted -keto(thio)esters are the most applied starting materials (cf. I), 6,10,15,20,23 followed by ()-halocinnamates (II), 16,17 arylpropiolates (Fiesselmann thiophene synthesis, III), 5,24 and bis(methylene-active)sulfides and oxalic esters (IV), 11,14,25 whereas only a few applications of aryldithioesters (V) 26 or of alkynyl vinyl ethers possessing hypervalent iodine (VI) 27 have been described (Scheme 1).…”

Section: Coomementioning

confidence: 99%

“…[4][5][6]21,22 Substituted -keto(thio)esters are the most applied starting materials (cf. I), 6,10,15,20,23 followed by ()-halocinnamates (II), 16,17 arylpropiolates (Fiesselmann thiophene synthesis, III), 5,24 and bis(methylene-active)sulfides and oxalic esters (IV), 11,14,25 whereas only a few applications of aryldithioesters (V) 26 or of alkynyl vinyl ethers possessing hypervalent iodine (VI) 27 have been described (Scheme 1). The syntheses of the 3-hydroxythiophene precursors, however, are often limited to suitably substituted acetoacetates and derivatives of ,-unsaturated acids as starting compounds.…”

Section: Coomementioning

confidence: 99%

Section: Coomementioning

confidence: 99%

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Bromoarylation of Methyl 2-Chloroacrylate under Meerwein Conditions for the Synthesis of Substituted 3-Hydroxythiophenes

et al. 2021

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Methyl 3-aryl-2-bromo-2-chloropropanoates can be prepared by Meerwein reaction from methyl 2-chloroacrylate and various arenediazonium salts under copper(II) bromide catalysis. The resulting readily available compounds were used as starting materials in reactions with substituted methanethiols for the construction of substituted 3-hydroxythiophenes which have not yet been accessible by other routes. Structural variety of the obtained 2-substituted 5-aryl-3-hydroxythiophenes has been achieved due to a wide range of available starting materials, including both anilines and thiols.

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Facile synthesis of new N1-alkylated 1H-indazole-3-carboxamide derivatives as potential anticancer agents: In vitro, ADMET prediction, and SAR studies

Puri

Juvale

2022

Journal of Molecular Structure

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Identification of protein kinase fibroblast growth factor receptor 1 (FGFR1) inhibitors among the derivatives of 5-(5,6-dimethoxybenzimidazol-1-yl)-3-hydroxythiophene-2-carboxylic acid

Cited by 5 publications

References 50 publications

Discovery of novel antituberculosis agents among 3-phenyl-5-(1-phenyl-1H-[1,2,3]triazol-4-yl)-[1,2,4]oxadiazole derivatives targeting aminoacyl-tRNA synthetases

Discovery of novel antituberculosis agents among 3-phenyl-5-(1-phenyl-1H-[1,2,3]triazol-4-yl)-[1,2,4]oxadiazole derivatives targeting aminoacyl-tRNA synthetases

Bromoarylation of Methyl 2-Chloroacrylate under Meerwein Conditions for the Synthesis of Substituted 3-Hydroxythiophenes

Facile synthesis of new N1-alkylated 1H-indazole-3-carboxamide derivatives as potential anticancer agents: In vitro, ADMET prediction, and SAR studies

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