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A series of novel 2-(pyridin-4-yl)quinazolin-4(3H)-ones bearing different heterocycle cores as potential PI3K inhibitors have been synthesized and evaluated via the MTT assay for their antiproliferative properties against selected HePG-2, MCF-7, and HCT116 cancer cell lines. Among them, compound 9 displayed significant activity against HePG-2 (IC50 = 60.29 ± 1.06 μM) comparable to doxorubicin as a reference anticancer drug (IC50 = 69.60 ± 1.50 μM). Kinase inhibitory assessment of target products against PI3K and docking studies revealed the promising binding affinities which match with the binding mode of the ligand, SW13 towards the active site of PI3K. Therefore, this work represents a promising matrix for developing novel potential anticancer candidates.

PI3K Inhibitors of Novel Hydrazide Analogues Linked 2-Pyridinyl Quinazolone Scaffold as Anticancer Agents