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Synthesis, anticancer and apoptosis-inducing activities of quinazoline-isatin conjugates: epidermal growth factor receptor-tyrosine kinase assay and molecular docking studies.

ABSTRACT: A new series of quinazolinone compounds 16-34 incorporating isatin moieties was synthesized. The antitumor efficacy of the compounds against MDA-MB-231, a breast cancer cell line, and LOVO, a colon cancer cell line, was assessed. Compounds 20, 21, 22, 23, 25, 27, 28, 29, 30, 31, 32, 33, and 34 displayed potent antitumor activity against MDA-MB-231 and LOVO cells (IC50: 10.38-38.67??M and 9.91-15.77??M, respectively); the comparative IC50 values for 5-fluorouracil and erlotinib in these cells lines were 70.28??M, 22.24??M and 15.23??M, 25.31??M respectively. The EGFR-TK assay and induction of apoptosis for compound 31 were investigated to assess its potential cytotoxic activity as a representative example of the novel synthesized compounds. At a concentration of 10??M, compound 31 exhibited efficient inhibitory effect against EGFR-TK and induced apoptosis in MDA-MB-231 cells. Furthermore, a molecular docking study for compound 31 and erlotinib was performed to verify the binding mode toward the EGFR kinase enzyme, and showed a similar interaction as that with erlotinib alone. Graphical Abstract: Compound 31 showed potent antitumor activity and efficient inhibitory effect against EGFR-TK and induced apoptosis of MDA-MB-231 cells at a concentration of 10??M.

SUBMITTER: El-Azab AS

PROVIDER: S-EPMC6445199 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Synthesis, anticancer and apoptosis-inducing activities of quinazoline-isatin conjugates: epidermal growth factor receptor-tyrosine kinase assay and molecular docking studies.

El-Azab Adel S AS Al-Dhfyan Abdullah A Abdel-Aziz Alaa A-M AA Abou-Zeid Laila A LA Alkahtani Hamad M HM Al-Obaid Abdulrahman M AM Al-Gendy Manal A MA

Journal of enzyme inhibition and medicinal chemistry 20171201 1

A new series of quinazolinone compounds 16-34 incorporating isatin moieties was synthesized. The antitumor efficacy of the compounds against MDA-MB-231, a breast cancer cell line, and LOVO, a colon cancer cell line, was assessed. Compounds 20, 21, 22, 23, 25, 27, 28, 29, 30, 31, 32, 33, and 34 displayed potent antitumor activity against MDA-MB-231 and LOVO cells (IC<sub>50</sub>: 10.38-38.67 μM and 9.91-15.77 μM, respectively); the comparative IC<sub>50</sub> values for 5-fluorouracil and erloti ...[more]

PMID: 28718672

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Dataset Information

Synthesis, anticancer and apoptosis-inducing activities of quinazoline-isatin conjugates: epidermal growth factor receptor-tyrosine kinase assay and molecular docking studies.

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Synthesis, anticancer and apoptosis-inducing activities of quinazoline-isatin conjugates: epidermal growth factor receptor-tyrosine kinase assay and molecular docking studies.

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