Synthesis of some quinazolinones inspired from the natural alkaloid L<i>-</i>norephedrine as EGFR inhibitors and radiosensitizers
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A set of quinazolinones synthesized by the aid of L-norephedrine was assembled to generate novel analogues as potential anticancer and radiosensitizing agents. The new compounds were evaluated for their cytotoxic activity against MDA-MB-231, MCF-7, HepG-2, HCT-116 cancer cell lines and EGFR inhibitory activity. The most active compounds <b>5</b> and <b>6</b> were screened against MCF-10A normal cell line and displayed lower toxic effects. They proved their relative safety with high selectivity towards MDA-MB-231 breast cancer cell line. Measurement of the radiosensitizing activity for <b>5</b> and <b>6</b> revealed that they could sensitize the tumour cells after being exposed to a single dose of 8 Gy gamma radiation. Compound <b>5</b> was able to induce apoptosis and arrest the cell cycle at the G2-M phase. Molecular docking of <b>5</b> and <b>6</b> in the active site of EGFR was performed to gain insight into the binding interactions with the key amino acids.
