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.
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
