Design, synthesis and biological evaluation of some novel quinazolinone derivatives as potent apoptotic inducers.

AIM: Novel quinazolinone and triazinoquinazolinone derivatives were designed and synthesized as apoptotic inducers.

METHODOLOGY/RESULTS: Most of the synthesized compounds showed excellent antiproliferative activity against MCF-7 and HCT-116 cell lines, respectively. Compounds 7a, 8a, 8d, 14a and 14d were superior to doxorubicin as activators of caspases 3, 8 and 9 in HCT-116 cell line. The most potent caspase inducers, 8d and 14a showed cell cycle arrest mainly in G1 and S phase, respectively and increased the levels of p53, Bax and the Bax/Bcl-2 ratio compared with doxorubicin in HCT-116 cells with excellent selectivity against CCD-18Co human colon normal cell line.

CONCLUSION: The synthesized compounds can be considered as potent apoptotic inducers interfering with extrinsic and intrinsic apoptotic pathways.