Indole-fused benzooxazepines: a new structural class of anticancer agents
Ashok K Singh1, Vinit Raj1, Amit Rai1
1Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Rae Bareli Road, Lucknow 226025, India.
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.
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