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Synthesis, characterization, crystal structures, and anticancer activity of some new 2,3-dihydro-1,5-benzoxazepines

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Abstract

Various benzoxazepine derivatives have been synthesized and characterized using IR, NMR, GC–MS, and microanalysis. The single-crystal X-ray structures of 2,2-dimethyl-4-[(E)-2-(4-methylphenyl)ethenyl]-2,3-dihydro-1,5-benzoxazepine (RS01), 4-[(E)-2-(2-chlorophenyl)ethenyl] -2,2-dimethyl-2,3-dihydro-1,5-benzoxazepine (RS05), 2,2,4-trimethyl-2,3-dihydrobenzothiazepine (RS11), and 2,2,4-trimethyl-2,3-dihydrobenzoxazepine (RS12) have been discussed. The compounds have been evaluated for their anticancer properties in breast cancer cells. 4-[(E)-2-(2-Chlorophenyl)ethenyl]-2,2-dimethyl-2,3-dihydro-1,5-benzoxazepine (RS03) and RS12 displayed potent cytotoxicity in both benign (MCF-7) and metastatic (MDA-MB-231) breast cancer cells. These compounds were more selective for the MCF-7 cells with RS03 being the most potent compound (IC50 = 15 µM) of the series. Upon further investigation, it was found that RS03 and RS12 induced cell cycle arrest in the G2/M phase and display limited toxicity against the noncancerous breast cell line, MCF-10A.

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Acknowledgements

F. Odame thanks the National Research Foundation for awarding him a Postdoctoral Fellowship. R. Schoeman would like to acknowledge Nelson Mandela University and National Research Foundation for the MSc Scholarship.

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  1. These authors contributed equally: Felix Odame, Recardia Schoeman

Authors and Affiliations

  1. Department of Basic Sciences, University of Health and Allied Sciences, PMB 31, Ho, Ghana

    Felix Odame

  2. Department of Chemistry, Nelson Mandela University, P.O. Box 77000, Port Elizabeth, 6031, South Africa

    Felix Odame, Eric C. Hosten & Zenixole R. Tshentu

  3. Department of Biochemistry and Microbiology, Nelson Mandela University, P.O. Box 77000, Port Elizabeth, 6031, South Africa

    Recardia Schoeman, Jason Krause & Carminita Frost

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Odame, F., Schoeman, R., Krause, J. et al. Synthesis, characterization, crystal structures, and anticancer activity of some new 2,3-dihydro-1,5-benzoxazepines. Med Chem Res 30, 987–1004 (2021). https://doi.org/10.1007/s00044-021-02706-9

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