174869-09-1Relevant articles and documents
Quinazolin-4(3H)-one based potential multiple tyrosine kinase inhibitors with excellent cytotoxicity
Mirgany, Tebyan O.,Abdalla, Ashraf N.,Arifuzzaman, Md,Motiur Rahman,Al-Salem, Huda S.
, p. 2055 - 2067 (2021/09/28)
A series of quinazolin-4(3H)-one derivatives were synthesised and evaluated for their cytotoxicity against human Caucasian breast adenocarcinoma (MCF-7) and human ovarian carcinoma (A2780) cell lines. Cytotoxicity of the most tested compounds was 2- to 30-fold more than the positive control lapatinib (IC50 of 2j = 3.79 ± 0.96; 3j = 0.20 ± 0.02; and lapatinib = 5.9 ± 0.74) against MCF7 cell lines except two compounds (IC50 of 2 b = 15.72 ± 0.07 and 2e = 14.88 ± 0.99). On the other hand, cytotoxicity was 4 ? 87 folds (IC50 of 3a = 3.00 ± 1.20; 3 g = 0.14 ± 0.03) more the positive control lapatinib (IC50 = 12.11 ± 1.03) against A2780 cell lines except compound 2e (IC50 = 16.43 ± 1.80). Among the synthesised quinazolin-4(3H)-one derivatives, potent cytotoxic 2f-j and 3f-j were investigated for molecular mechanism of action. Inhibitory activities of the compounds were tested against multiple tyrosine protein kinases (CDK2, HER2, EGFR and VEGFR2) enzymes. As expected, all the quinazolin-4(3H)-one derivatives were showed comparable inhibitory activity against those kinases tested, especially, compound 2i and 3i showed potent inhibitory activity against CDK2, HER2, EGFR tyrosine kinases. Therefore, molecular docking analysis for quinazolin-4(3H)-one derivatives 2i and 3i were performed, and it was revealed that compounds 2i and 3i act as ATP non-competitive type-II inhibitor against CDK2 kinase enzymes and ATP competitive type-I inhibitor against EGFR kinase enzymes. However, in case of HER2, compounds 2i act as ATP non-competitive type-II inhibitor and 3i act as ATP competitive type-I inhibitor. Docking results of known inhibitors were compared with synthesised compounds and found synthesised 2i and 3i are superior than the known inhibitors in case of interactions. In addition, in silico drug likeness properties of quinazolin-4(3H)-one derivatives showed better predicted ADME values than lapatinib.
Design, Synthesis, Anticancer Activity, and Cell Cycle Analysis of Novel Quinazoline Derivatives Targeting VEGFR-2 Kinase
Ahmed, Marwa F.,Eed, Emad M.,Khalifa, Amany S.
, p. 2497 - 2505 (2022/01/22)
Abstract: Novel quinazoline derivatives have been designed, synthesized and tested for cytotoxic activity against HCT116, and MCF-7 cell lines. The preliminary data indicate their promising antitumor potential. Enzyme inhibitory activity of the most active product against VEGFR-2 has been assessed. Apoptosis and cell cycle arrest during the G2/M phase has been triggered by the product, and according to the gene expression data, it increases BAX and caspase-3 expression while decreasing Bcl-2 expression.
2-thioquinazolinone compound and preparation method and application thereof
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Paragraph 0053; 0098-0104, (2021/09/08)
The invention provides a 2-thioquinazolinone compound and a preparation method and application thereof, and belongs to the technical field of organic synthesis. The preparation method comprises the following steps: mixing an anthranilamide compound, an isothiocyanate compound, a bromide and a polar organic solvent, and carrying out a series cyclization reaction in an air atmosphere to obtain the 2-thioquinazolinone compound. According to the preparation method, the 2-thioquinazolinone compound can be prepared by one-step reaction without adding a catalyst, the yield and the purity of the product are high, the reaction route is simple, the operation is simple, and the preparation method is suitable for industrial production.
Synthesis, anticonvulsant activity and molecular modeling study of some new hydrazinecarbothioamide, benzenesulfonohydrazide, and phenacylacetohydrazide analogues of 4(3H)-quinazolinone
Al-Salem, Huda S.A.,Hegazy, Gehan H.,El-Taher, Kamal E.H.,El-Messery, Shahenda M.,Al-Obaid, Abdulrahman M.,El-Subbagh, Hussein I.
, p. 1490 - 1499 (2015/03/30)
A new series of quinazoline analogues was designed and synthesized to get the target compounds 18-21, 30-41, 46-53, and 57-76. The Obtained compounds were evaluated for their anticonvulsant activity using PTZ and picrotoxin convulsive models. Compounds 47, 63, 68 and 73 proved to be the most active compounds in this study with a remarkable 100% protection against PTZ induced convulsions. Compounds 47, 63, 68 and 73 proved to be 10, 4, 4, and 5 fold more active, respectively than the used positive control sodium valproate. Structure activity correlation concluded valuable pharmacophoric information which confirmed by molecular modeling studies. Molecular docking study of 68 suggested its agonistic behavior toward GABAA receptor. The studied quinazoline analogues could be considered as useful templates for future development and further derivatization.
Synthesis and anticonvulsant activity of new acylthiosemicarbazides and thiazolidines
Gursoy,Karali
, p. 857 - 866 (2007/10/03)
A number of 1-(3-phenyl-4(3H)-quinazolinone-2-ylmercaptoacetyl)-4-substituted thiosemicarbazide and 2-(3-phenyl-4(3H)-quinazolinone-2-ylmercaptoacetylhydrazono)-3-substit uted 4-thiazolidone derivatives were synthesized and evaluated for anticonvulsant ac
