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Morpholine substituted quinazoline derivatives as anticancer agents against MCF-7, A549 and SHSY-5Y cancer cell lines and mechanistic studies.

A series of morpholine substituted quinazoline derivatives have been synthesized and evaluated for cytotoxic potential against A549, MCF-7 and SHSY-5Y cancer cell lines. These compounds were found to be non-toxic against HEK293 cells at 25 μM and hence display anticancer potential. In these series compounds, AK-3 and AK-10 displayed significant cytotoxic activity against all the three cell lines. AK-3 displayed IC50 values of 10.38 ± 0.27 μM, 6.44 ± 0.29 μM and 9.54 ± 0.15 μM against A549, MCF-7 and SHSY-5Y cancer cell lines. Similarly, AK-10 showed IC50 values of 8.55 ± 0.67 μM, 3.15 ± 0.23 μM and 3.36 ± 0.29 μM against A549, MCF-7 and SHSY-5Y, respectively. In the mechanistic studies, it was found that AK-3 and AK-10 inhibit the cell proliferation in the G1 phase of the cell cycle and the primary cause of death of the cells was found to be through apoptosis. Thus, morpholine based quinazoline derivatives have the potential to be developed as potent anticancer drug molecules.