Background:
Cancer is a life-threatening group of diseases and universally the second main cause of death. Design and
development of new scaffolds targeting selective cancer cells is considered a promising goal for cancer treatment.
Aim 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 is to further investigate the anticancer activities of the chalcone derivatives against human colon cancer cells with possible
elucidation of their mechanism of action.
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.
Discovery of 4H-chromeno[2,3-d]pyrimidin-4-one derivatives as senescence inducers and their senescence-associated antiproliferative activities on cancer cells using advanced phenotypic assay
