Abstract
In this study, 12 novel polyphenols containing the quinazolin-4(3H )-one ring were synthesized and characterized using 1 H/13 C NMR and HRMS analyses, yielding the target compounds in excellent yields (88–96%).
Biological evaluation revealed significant cytotoxic activity against PC3 prostate
cancer and 3T3 fibroblast cell lines, with compounds 2,2′-(propane-1,3-diyl)bis-3-(2,4-dihydroxybenzylideneamino)quinazolin-4(3H )-one (5 ) and 2,2′-(propane-1,3-diyl)bis-3-(2,3,4-trihydroxybenzylideneamino)quinazolin-4(3H )-one (6 ) demonstrating the highest anticancer potential. Compound 6 exhibited the highest selectivity (IC50 = 5.72 µM, SI = 68), outperforming the reference drug, doxorubicin. In silico studies, including molecular docking and dynamics simulations, showed strong binding
affinities for mTOR, P110α, and PARP1, particularly for compound 6 . Key interactions, such as hydrogen bonds and π-π stacking, contributed to the stability
of the 6 –mTOR complex. These results highlight compounds 5 and 6 as promising candidates for prostate cancer therapy, with compound 6 showing superior selectivity and interaction profiles, providing the groundwork for
further preclinical development.
Key words hydrazone - quinazolin-4(3
H )-one - prostate cancer - cytotoxicity - molecular docking - molecular dynamics
