Purin-6-one and pyrrolo[2,3-d]pyrimidin-4-one derivatives as potentiating agents of doxorubicin cytotoxicity
Abstract
Aim: DNA damage response plays an eminent role in patients' response to conventional chemotherapy and radiotherapy. Its inhibition is of great interest as it can overcome cancer cell resistance and reduce the effective doses of DNA damaging agents.
Results & methodology: We have focused our research on phos-phatidylinositol 3-kinase-related kinases and prepared 35 novel compounds through a scaffold hopping approach. The newly synthesized inhibitors were tested on a panel of nine cancer and one healthy cell lines alone and in combination with appropriate doses of doxorubicin.
Conclusion: Five novel compounds 4f, 10b, 15g, 7e and 15f in combination with doxorubicin showed significant antiproliferative effect on seven cancer cell lines while not affecting the cell growth alone.