Cyclisation reaction between 3-methylquinoxaline-2-thione and benzaldehydes into 3-benzyl-2-aryl-thieno[2,3-b]quinoxaline promoted by Brønsted acids

Saoudi, Besma; Téniou, Abderrahmane; Debache, A.; Roisnel, Thierry; Soulé, Jean‐François

doi:10.1016/j.crci.2015.06.003

Cited by 9 publications

(10 citation statements)

References 18 publications

(14 reference statements)

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“…Esters derivatives 2a and 2b were obtained by the Fischer esterification reaction of the commercially available 4-methylbenzoic acid 1a and 4-chlorobenzoic acid 1b with absolute ethanol in the presence of the dehydrating conc. Sulfuric acid as a catalyst [ 24 , 25 ]. Condensation of the above ester derivatives with hydrazine hydrate in refluxing ethanol, following the reported procedures, furnished the target hydrazide derivatives 3a,b [ 24 , 25 ].…”

Section: Resultsmentioning

confidence: 99%

“…Condensation of the above ester derivatives with hydrazine hydrate in refluxing ethanol, following the reported procedures, furnished the target hydrazide derivatives 3a,b [ 24 , 25 ]. In a parallel pathway, anthranilic acid 4 was heated in an aqueous solution of potassium cyanate with a catalytic amount of glacial acetic acid to produce quinazoline-2,4(1 H ,3 H )-dione 5 [ 24 , 25 ]. Chlorination of 5 using phosphorus oxychloride and triethyl amine (TEA) afforded 2,4-dichloroquinazoline 6 [ 24 , 25 ].…”

Section: Resultsmentioning

confidence: 99%

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New [1,2,4]triazolo[4,3-c]quinazolines as intercalative Topo II inhibitors: Design, synthesis, biological evaluation, and in silico studies

Gaber

Sobhy²,

Turky³

et al. 2023

PLoS ONE

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Fifteen quinazoline derivatives were designed and synthesized as DNA intercalators. The cytotoxicity of the designed members was assessed against HCT-116 and HepG2 cancer cell lines. In addition, the topoisomerase II (Topo II) inhibitory effect was assessed. Compound 16 was the most cytotoxic and Topo II inhibitor with low cytotoxicity against Vero cells. Compounds 16, 17, and 18 showed significant DNA binding affinities. Compound 16 showed Topo II catalytic inhibitory effect at a concentration of 10 μM. Further mechanistic investigations revealed the capability of compound 16 to induce apoptosis in HCT-116 cells and arrest the growth at the S and G2/M phases. Also, compound 16 showed a significant increase in the level of BAX (2.18-fold) and a marked decrease in the level of Bcl-2 (1.9-fold) compared to the control cells. In silico studies revealed the ability of the synthesized members to bind to the DNA-Topo II complex.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

New [1,2,4]triazolo[4,3-c]quinazolines as intercalative Topo II inhibitors: Design, synthesis, biological evaluation, and in silico studies

Gaber

Sobhy²,

Turky³

et al. 2023

PLoS ONE

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“…Chlorination of compound 11 was achieved using phosphorous oxychloride to afford 2-chloro-3-methylquinoxaline 13 68 . Refluxing the latter with thiourea in absolute ethanol resulted in 3-methylquinoxaline-2-thiol 14 69 , 70 which was underwent heating with alcoholic potassium hydroxide to provide the corresponding potassium salt 15 ( Scheme 1 ).…”

Section: Resultsmentioning

confidence: 99%

“…All the reagents, chemicals, and apparatus were presented in Supplementary Data . Compounds 11 67 , 12 67 , 13 68 , 14 69 , 70 , 15 69 , 70 , and the intermediates ( 24a , b , 25 , 26a–j ) 63 , 64 were prepared according to the reported procedures.…”

Section: Methodsmentioning

confidence: 99%

Design, synthesis, docking, ADMET studies, and anticancer evaluation of new 3-methylquinoxaline derivatives as VEGFR-2 inhibitors and apoptosis inducers

Alanazi

Eissa

Alsaif

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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Vascular endothelial growth factor receptor-2 (VEGFR-2) plays a critical role in cancer angiogenesis. Inhibition of VEGFR-2 activity proved effective suppression of tumour propagation. Accordingly, two series of new 3-methylquinoxaline derivatives have been designed and synthesised as VEGFR-2 inhibitors. The synthesised derivatives were evaluated in vitro for their cytotoxic activities against MCF-7and HepG2 cell lines. In addition, the VEGFR-2 inhibitory activities of the target compounds were estimated to indicate the potential mechanism of their cytotoxicity. To a great extent, the results of VEGFR-2 inhibition were highly correlated with that of cytotoxicity. Compound 27a was the most potent VEGFR-2 inhibitor with IC 50 of 3.2 nM very close to positive control sorafenib (IC 50 = 3.12 nM). Such compound exhibited a strong cytotoxic effect against MCF-7 and HepG2, respectively with IC 50 of 7.7 and 4.5 µM in comparison to sorafenib (IC 50 = 3.51 and 2.17 µM). In addition, compounds 28 , 30f , 30i , and 31b exhibited excellent VEGFR-2 inhibition activities (IC 50 range from 4.2 to 6.1 nM) with promising cytotoxic activity. Cell cycle progression and apoptosis induction were investigated for the most active member 27a . Also, the effect of 27a on the level of caspase-3, caspase-9, and BAX/Bcl-2 ratio was determined. Molecular docking studies were implemented to interpret the binding mode of the target compounds with the VEGFR-2 pocket. Furthermore, toxicity and ADMET calculations were performed for the synthesised compounds to study their pharmacokinetic profiles

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“…Subsequent heating of compound 3 with alcoholic potassium hydroxide gave the corresponding potassium salt 4 44 . To prepare 3-methylquinoxaline-2-thiol 5 , the previously prepared 3-methylquinoxalin-2(1 H )-one 3 was refluxed with P 2 S 5 in pyridine as a solvent, then the reaction was acidified using HCl 45 , 46 . Heating of compound 5 with alcoholic potassium hydroxide gave the corresponding potassium salt 6 ( Scheme 1 ).…”

Section: Resultsmentioning

confidence: 99%

Discovery of new 3-methylquinoxalines as potential anti-cancer agents and apoptosis inducers targeting VEGFR-2: design, synthesis, and in silico studies

Alanazi

Elwan

Alsaif

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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There is an urgent need to design new anticancer agents that can prevent cancer cell proliferation even with minimal side effects. Accordingly, two new series of 3-methylquinoxalin-2(1 H )-one and 3-methylquinoxaline-2-thiol derivatives were designed to act as VEGFR-2 inhibitors. The designed derivatives were synthesised and evaluated in vitro as cytotoxic agents against two human cancer cell lines namely, HepG-2 and MCF-7. Also, the synthesised derivatives were assessed for their VEGFR-2inhibitory effect. The most promising member 11e were further investigated to reach a valuable insight about its apoptotic effect through cell cycle and apoptosis analyses. Moreover, deep investigations were carried out for compound 11e using western-plot analyses to detect its effect against some apoptotic and apoptotic parameters including caspase-9, caspase-3, BAX, and Bcl-2. Many in silico investigations including docking, ADMET, toxicity studies were performed to predict binding affinity, pharmacokinetic, drug likeness, and toxicity of the synthesised compounds. The results revealed that compounds 11e, 11g, 12e, 12g, and 12k exhibited promising cytotoxic activities (IC 50 range is 2.1 − 9.8 µM), comparing to sorafenib (IC 50 = 3.4 and 2.2 µM against MCF-7 and HepG2, respectively). Moreover, 11b, 11f, 11g, 12e, 12f, 12g, and 12k showed the highest VEGFR-2 inhibitory activities (IC 50 range is 2.9 − 5.4 µM), comparing to sorafenib (IC 50 = 3.07 nM). Additionally, compound 11e had good potential to arrest the HepG2 cell growth at G2/M phase and to induce apoptosis by 49.14% compared to the control cells (9.71%). As well, such compound showed a significant increase in the level of caspase-3 (2.34-fold), caspase-9 (2.34-fold), and BAX (3.14-fold), and a significant decrease in Bcl-2 level (3.13-fold). For in silico studies, the synthesised compounds showed binding mode similar to that of the reference compound (sorafenib).

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Cyclisation reaction between 3-methylquinoxaline-2-thione and benzaldehydes into 3-benzyl-2-aryl-thieno[2,3-b]quinoxaline promoted by Brønsted acids

Cited by 9 publications

References 18 publications

New [1,2,4]triazolo[4,3-c]quinazolines as intercalative Topo II inhibitors: Design, synthesis, biological evaluation, and in silico studies

New [1,2,4]triazolo[4,3-c]quinazolines as intercalative Topo II inhibitors: Design, synthesis, biological evaluation, and in silico studies

Design, synthesis, docking, ADMET studies, and anticancer evaluation of new 3-methylquinoxaline derivatives as VEGFR-2 inhibitors and apoptosis inducers

Discovery of new 3-methylquinoxalines as potential anti-cancer agents and apoptosis inducers targeting VEGFR-2: design, synthesis, and in silico studies

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