Background: Phosphatidylinositol-3-kinase α (PI3Kα) is a ubiquitous intracellular enzyme, mainly
involved in intracellular signaling pathways, promotes cellular growth, proliferation, and differentiation. Therefore,
inhibition of PI3K can be a hotspot in molecular targeted therapy for the treatment of cancer.
Methods: The present research work involves molecular docking studies performed to screen derivatives of urea
and thiourea bearing thieno [3,2-d]-pyrimidines against the active site of PI3K enzyme using MOE.2008.10. The
designed structures (6a-f) and (7a-j) were synthesized by the facile synthetic methods and evaluated for their
anticancer activity against HT-29 and MCF-7 cell lines and inhibitory activity against PI3Kα enzyme.
Results: Among the tested compounds, 4-(4-(2-(3-(pyrimidin-2-yl)thioureido)ethyl)piperazin-1-yl)thieno[3,2-
d]pyrimidine-6-carboxamide (7f) showed the highest anticancer activity against HT-29 and MCF-7 cell lines
with IC50 values of 2.18 µM and 4.25 µM, respectively. Further, the same compound also exhibited potent
PI3Kα inhibitory activity with IC50 value of 1.26 µM.
Conclusion: Docking studies supported the initial pharmacophoric hypothesis and suggested a mode of interaction
at the active binding site of PI3Kα, demonstrating that the target compounds were potential inhibitory
agents for cancer therapy.