Synthesis, antiradical, and antimicrobial activities of new pteridine‐2,4,7‐trione derivatives

Kazunin, M. S.; Voskoboynik, О. Yu.; Носуленко, И. С.; Берест, Г. Г.; Kholodniak, Sergiy; Pryymenko, Boris O.; Коваленко, С. И.

doi:10.1002/jhet.3774

Cited by 5 publications

(7 citation statements)

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“…[ 14,15 ] Synthesis of substituted 2‐thioxo‐2,3‐dihydropteridin‐4(1 H )‐ones ( 2 ) was conducted via condensation of substituted 5,6‐diamino‐2‐thioxo‐2,3‐dihydropyrimidin‐4(1 H )‐ones ( 1 ) with carbonyl compounds or ketocarboxylic acids (Scheme 1). [ 9–11 ] The formation of the thio‐containing pteridines was proved by the presence of signals of protons at nitrogen in positions N1 and N3 that were observed at the 13.31–12.24 ppm and 12.7–10.87 ppm correspondingly. Additionally, 1 H NMR spectra of compounds 2.3–2.5 were characterized by signals of hydroxy‐group protons in 7th position at the 13.72–13.33 ppm, and compounds 2.4 , 2.5 , by signals of carboxylic groups protons at the 11.94–11.79 ppm.…”

Section: Resultsmentioning

confidence: 99%

“…The Synthesis of propionamides 5 was conducted by a previously described procedure [11] that was based on the reaction between anilines or amino acids and obtained in situ lactones (A) (Scheme 2). [9][10][11] The structures of compound 5 were proven by the presence of signals that correspond to the protons at the nitrogen atom, that were registered at the 8.08-7.95 ppm for aliphatic amides (compounds 5.1-5.3) or at the 9.88 and 10.21 ppm for aromatic amines (compounds 5.4, 5.5). The signals of carboxy alkyl moiety (for compounds 5.1-5.3) and aromatic fragment (for compounds 5.4, 5.5) were observed as well.…”

Section: Chemistrymentioning

confidence: 99%

“…Thus, thio-containing pteridines are promising biologically active compounds and can be used for the treatment of widespread and severe diseases including cancer, inflammatory processes, and neurodegenerative pathologies. The present paper is a sequel to our previous investigations aimed at the search for biologically active compounds among substituted pteridines [9][10][11][12] and is devoted to the search for DHFR inhibitors among a series of thio-contained pteridines that are structurally similar to the known medicines with this mechanism of action (Figure 1). [13] Evaluation of radical-scavenging activity of obtained compounds was the additional aim of the present study.…”

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Тhio‐containing pteridines: Synthesis, modification, and biological activity

Kazunin

Groma

Носуленко

et al. 2022

Archiv der Pharmazie

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The present article is devoted to searching for biologically active agents among novel thio-containing pteridines. Synthetic protocols based on the condensation of 5,6diamino-2-thioxo-2,3-dihydropyrimidin-4(1H)-ones with dicarbonyl compounds were elaborated and used for the synthesis of target products. The directions for further modification of the obtained thio-containing pteridines were substantiated and realized. The spectral properties of the obtained compounds were studied and described. The results of the in silico study revealed that the predicted affinity of the obtained compounds to the dihydrofolate reductase (DHFR) active site is comparable with the affinity of methotrexate, despite the differences in the nature of the ligand-enzyme interactions. The in vitro study of DHFR-inhibiting activity revealed that the most active compounds 3.9 and 4.2 have lg IC 50 values of −5.889 and −5.233, respectively, significantly inferior to methotrexate (lg IC 50 = −7.605).Additionally, the synthesized compounds were studied for their antiradical activity as a possible mechanism of pharmacological effects. Among the obtained pteridines, compounds 5.1 (lg EC 50 = −4.82) and 5.3 (lg EC 50 = −4.92) have antiradical activity higher than the reference compound ascorbic acid (lg EC 50 = −4.81). The conducted structure-activity relationship analysis provided valuable data for the further search for biologically active agents among thio-containing pteridines and related compounds.

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Section: Resultsmentioning

confidence: 99%

Section: Chemistrymentioning

confidence: 99%

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confidence: 99%

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Тhio‐containing pteridines: Synthesis, modification, and biological activity

Kazunin

Groma

Носуленко

et al. 2022

Archiv der Pharmazie

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“…6-Substituted 1-methylpteridine-2,4,7-triones (2.1-2.5, 3.1-3.14, 4.1-4.2), 1-methyl-7-arylfuro[3,2-g]pteridine-2,4(1H,3H)-diones (5.1-5.3) and butyl 2-(1-methyl-2,4-dioxo-7-aryl-1,4-dihydrofuro[3,2-g]pteridine-3(2H)-yl)acetates (6.1-6.8) were selected for screening the DHFR-inhibitory activity. The synthesis and physicochemical data of the tested compounds were described previously [20][21][22].…”

Section: Methodsmentioning

confidence: 99%

Dihydrofolate reductase inhibitors among pteridine and fu-ro[3,2-g]pteridine derivatives

et al. 2021

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To the purposeful search for the DHFR-inhibitors among substituted pteridine-2,4,7triones and 7-aryl-(hetaryl-)furo[3,2-g]pteridine-2,4(1H,3H)-diones for further biological research. Methods. In vitro methods, molecular docking, SAR-analysis, statistical methods. Results. The DHFR-inhibitory activity of substituted 1-methylpteridine-2,4,7-triones (2, 3, 4) and 7-aryl-(hetaryl-)furo[3,2-g]pteridine-2,4(1H,3H)-diones (5, 6) was studied. It was estab- 6) inhibited DHFR by 14.59-52.11 %, and were less active comparing to methotrexate. It was found that the introduction of aryl moiety with electron-accepting group, naphthyl substituent or electron-accepting heterocycle (furan, thiophene and benzofuran) caused an increase in the DHFR-inhibitory activity. Additionally, it was shown, that annulation of the furan cycle to the pteridine system was reasonable in the scope of new DHFR-inhibitors synthesis. Thereby it may be concluded that the calculated values of affinity are not reliable predictors for the DHFR-inhibiting activity of studied compound. However, the molecular docking study may be used for evaluation of the interactions between the studied inhibitor and active center of DHFR. Conclusions. The conducted primary in vitro screening revealed low or moderate DHFR-inhibiting activity of the synthesized compounds. The visualization of molecular docking showed that despite the structural similarity to methotrexate, the obtained compounds form different ligand-enzyme interactions. The calculated values of affinity cannot be used as predictors of DHFR-inhibiting activity because of the absence of correlation between the abovementioned indicators. The obtained compounds may be of interest for further studies aimed at the search for anti-inflammatory, anti-viral, hypoglycemic, hypotensive, anti-ische mic agents due to the expected low-toxicity associated with the slight DHFR-inhibiting activity.

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“…As a result, the term antioxidant has emerged, compounds that reduce and prevent the effects of free radicals. Most of the newly synthesized substances are studied for their antiradical properties [1][2][3]. 1,2,4-Triazole derivatives are no exception [4], which have already proven themselves as biologically active compounds [5][6][7][8][9][10].…”

Section: актуальные вопросы фармацевтической и медицинской науки и практики 2021 т 14 № 2(36) с 162-166mentioning

confidence: 99%

Antiradical activity of novel 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol derivatives

Сафонов

Носуленко

2021

АПФМНП

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The process of studying free radicals began in the middle of the last century (the free radical theory of aging in 1956). Multiple studies have revealed the effect of free radicals on the cells of the body and the development of various diseases, such as diabetes, autoimmune diseases, diseases of the nervous system, and others. As a result, the term antioxidant has emerged, compounds that reduce and prevent the effects of free radicals. Most of the newly synthesized substances are studied for their antiradical properties. 1,2,4-Triazole derivatives are no exception, which has already proven themselves as biologically active compounds. The aim of this work was the investigation antiradical activity among 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol derivatives. Materials and methods. Previously synthesized 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol derivatives were used as test compounds. The research of antiradical activity was based on the interaction between 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol derivatives and 2,2-diphenyl-1-picrylhydrazyl (DPPH) in vitro. DPPH is a stable free radical. The color of its alcoholic solutions were intense purple (λmax = 517 nm). When DPPH interacted with compounds that were capable of scavenging free radicals, it produced products. These products are yellow in color and do not absorb light of the aforementioned wavelength. The study was carried out according to the method. Results. The antiradical activity of 10 new 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol derivatives was studied. Most of the test compounds show antiradical activity against DPPH. Compound 1 was the most active at a concentration of 1 × 10-3 M and the antiradical effect was close to ascorbic acid. Conclusions. The most active compound is 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol, which in a concentration of 1 × 10-3 M has an antiradical effect in 88.89 %. When reducing the concentration to 1 × 10-4 M, also reduces the antiradical activity to 53.78 %. Some conclusions are drawn regarding the “structure – effect” dependence between 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol derivatives: – the introduction of 4-fluorobenzylidene radical (compound 2) into the 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol molecule results in a slight decrease in activity; – the introduction of 2-hydroxybenzylidene radical (compound 3) into initial molecule results a high antiradical effect, which hardly changes with decreasing concentration; – transformation to 2-((5-(thiophen-2-ylmethyl)-4-((R)amino)-4H-1,2,4-triazol-3-yl)thio)acetic acid has almost no effect on antiradical activity, except for compound 9 (the antiradical effect is reduse).

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Synthesis, antiradical, and antimicrobial activities of new pteridine‐2,4,7‐trione derivatives

Cited by 5 publications

References 15 publications

Тhio‐containing pteridines: Synthesis, modification, and biological activity

Тhio‐containing pteridines: Synthesis, modification, and biological activity

Dihydrofolate reductase inhibitors among pteridine and fu-ro[3,2-g]pteridine derivatives

Antiradical activity of novel 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol derivatives

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