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

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.