Synthesis of novel spirochromane incorporating Schiff's bases, potential antiproliferative activity, and dual EGFR/HER2 inhibition: Cell cycle analysis and study.

Spirochromanes incorporating Schiff's bases and semicarbazones and were synthesizedand analyzed for their potential antiproliferative activity using four human cancer cell lines (MCF-7, HCT-116, PC3, and A549). Compounds , and possessed the highest antiproliferative activity among the tested compounds,with an IC range of 1.154-9.09 μM. Compound selectively inhibited the PC3 cell proliferation (IC = 5.47 μM). Spirochromanes , and exhibited high inhibitory activity against EGFR (IC = 0.116, 0.132, and 0.077 μM, respectively) and HER2 (IC = 0.055, 0.210 and 0.085 μM, respectively) compared with the references, erlotinib (IC = 0.090 and 0.038 μM, respectively) and gefitinib (IC = 0.052 and 0.072 μM, respectively). Cell cycle analysis and apoptosis results showed that compounds , and arrested growth inthe S phase, and the programmed cell death induced by these compounds was an apoptotic mechanism rather than a necrotic pathway. Molecular docking studies of spirochromanes , and to EGFR and HER2 binding sites were performed to explore the orientation mode and interaction.