Aim: A new series of compounds (1a-16a) bearing indole-fused benzooxazepine was synthesized, characterized and evaluated for anticancer activity.
Materials & methods: In this study, all the synthesized compounds were screened via in vitro anticancer testing on Hep-G2 cancer cell line. A computational study was carried out on cancer-related targets including IL-2, IL-6, COX-2 Caspase-3 and Caspase-8.
Results: Some of the synthesized compounds effectively controlled the growth of cancerous cells.
Conclusion: The most active compounds - 6a, 10a, 13a, 14a and 15a - exemplify notable anticancer profile with GI50 <10 μg/ml. Preliminary structure-activity relationship among the tested compounds can produce an assumption that the electronegative groups at phenyl ring attached with indole-fused benzooxazepine are instrumental for the activity. Molecular docking study showed crucial hydrogen bond and π-π stacking interactions, with good ADMET profiling and molecular dynamic simulation.
Keywords: Hep-G2 cell lines; indole-fused benzooxazepines; interleukins and caspases; liver cancer; molecular docking and dynamics.