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Synthesis of novel benzothieno-[3,2’-f][1,3] oxazepines and their isomeric 2-oxo-2H-spiro[benzothiophene-3,3’-pyrrolines] via 1,4-dipolar cycloaddition reaction and their evaluation as cytotoxic anticancer leads

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Abstract

This study introduces a novel class of hybrid compounds, namely, benzothieno[3,2’-f][1,3]oxazepines and their isomeric 2-oxo-2H-spiro[benzothiophene-3,3’-pyrrolines]. The synthetic strategy employs a three-component reaction and 1,4-Dipolar cycloaddition, yielding spiro and oxazepine compounds. Structural elucidation via NMR and MS analyses is complemented by X-ray crystallography and a proposed mechanistic pathway. Biological evaluation against HEK-293 and HT-29 cells reveals potent and selective cytotoxicity against HEK-293 without cytotoxic effects against HT-29 cells. Compound 16c exhibited the highest cytotoxic properties with IC50 = 4.30 μM against HEK-293 cells. Accordingly, the new compounds can be considered as promising leads for possible optimization into novel selective cytotoxic treatments.

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Acknowledgements

We would like to thank the Deanship of Scientific Research at the University of Jordan, Amman-Jordan, for financial support.

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Correspondence to Areej M. Jaber or Mutasem O. Taha.

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Al-Mahadeen, M.M., Jaber, A.M., Zahra, J.A. et al. Synthesis of novel benzothieno-[3,2’-f][1,3] oxazepines and their isomeric 2-oxo-2H-spiro[benzothiophene-3,3’-pyrrolines] via 1,4-dipolar cycloaddition reaction and their evaluation as cytotoxic anticancer leads. Med Chem Res (2024). https://doi.org/10.1007/s00044-024-03229-9

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