Background: Cancer is a life-threatening group of diseases and universally, the second main cause of
death. The design and development of new scaffolds targeting selective cancer cells are considered a promising
goal for cancer treatment.
Aims and Objective: Chalcone derivatives; 6-(3-aryl-2-propenoyl)-2(3H)-benzoxazolone, were previously prepared
and evaluated against the oral cavity squamous cell carcinoma cell line, HSC-2, and were reported to have
remarkably high tumor selectivity. The aim of this study was to further investigate the anticancer activities of
the chalcone derivatives against human colon cancer cells with a possible elucidation of their mechanism of
Methods: Computational studies were conducted to explore the potential interaction of the synthesized molecules
with the phosphatidylinositol-4,5-bisphosphate 3-kinaseα (PI3Kα). Biological evaluation of the antiproliferative
activities associated with compounds 1-23 was carried out against the colon cancer cell line, HCT116.
Lactate Dehydrogenase (LDH) activity was measured to study necrosis, while the caspase-3 activation and DNA
measurements were used to evaluate apoptosis in the treated cells.
Results: Glide studies against PI3Kα kinase domain demonstrated that the 6-(3-aryl-2-propenoyl)-2(3H)-
benzoxazolone scaffold forms H-bond with K802, Y836, E849, V851, N853, Q859, and D933, and it fits the
fingerprint of PI3Kα active inhibitors. Biological evaluation of the reported compounds in HCT116 cell line
confirmed that the series inhibited PI3Kα activity and induced apoptosis via activation of caspase-3 and reduction
of DNA content.
Conclusion: The recently developed compounds might be employed as lead structures for the design of new
antitumor drugs targeting PI3Kα.