Novel 4-aminoquinazoline derivatives as new leads for anticancer drug discovery

A novel series of quinazoline derivatives 2-8, 10-12 were designed and synthesized. Structures of the newly synthesized compounds were confirmed by elemental analyses, IR, ¹H and ¹³C NMR spectral data. All the newly synthesized compounds were evaluated for in vitro cytotoxic activity against the breast cancer cell line MCF-7. Seven of the novel compounds exhibited higher activity than the reference drug doxorubicin. The corresponding compounds 3, 4, 5, 8, 10, 11 and 12 exhibited higher activity with IC₅₀ values from 22.75 to 43.44 μmol L⁻¹, compared to the reference drug doxorubicin with IC₅₀ value of 47.90 μmol L⁻¹. Also, compounds 1, 6, and 9 are nearly as active as doxorubicin with IC₅₀ values of 48.31, 48.90, and 48.91 μmol L⁻¹, respectively, while compounds 2 and 7 exhibited a moderate activity with IC₅₀ values of 50.44 and 52.37 μmol L⁻¹. In addition, compound 13 showed no activity. Cytotoxic screening of the tested copmpounds offered an encouraging framework that may lead to the discovery of potent anti-breast cancer activity.