QSAR-based Virtual Screening, Molecular Docking Synthesis and Biological Evaluation of Indole and Quinazolinone Hybrid Derivatives as PI3K Inhibitor for the Treatment of Cancer

Abstract A series of amino quinazolinone-indole hybrid molecules were designed. Molecular docking, physicochemical properties and toxicological studies were carried out before synthesizing the designed derivatives. Among the designed derivatives, 4 compounds were synthesized. All the synthesized compounds were characterized by TLC, IR, NMR, Mass spectroscopy. The biological activity tests were performed for 2 derivatives. The results of the MTT Assay state that the most potent derivative showed cytotoxic potential properties with an IC50 concentration at 97.13 μg/mL and the other compounds showed moderate toxicity with an IC50 value of 197.59 μg/mL after the incubation period of 24 hours. Among the given compounds, the leading compound caused effective cytotoxicity and anti-breast cancer effect with a relatively low IC50 value on MDA-MB-231 cells after 24 h of incubation. Doxorubicin showed an IC50 concentration of 2.26 μg/mL after an incubation period of 24 h, and the results of FACS apoptosis-necrosis states that the test compounds, with IC50 concentrations, significantly enhanced the 62.13 and 30.44% apoptosis in human breast cancer cells. The lead compound caused an effective apoptosis rate than the secondary molecule and a similar trend of necrosis rate, with 12 and 19.8%, respectively. Doxorubicin was used as a std control for the study, which showed 42.71% apoptosis and 30.4% necrosis, respectively.