Synthesis, characterization, antibacterial activity and cytotoxicity of (1R,2S,7aS)-2-(2,5-dichlorothiophene-3-carbonyl)-1-(aryl)-1,2,5, 6,7,7a-hexahydrospiro[indoline-3,3-pyrrolizin]-2-one derivatives

The synthesis and bioactivity studies of a series of (1 ' R,2 ' S,7a ' S)-2 '-(2,5-dichlorothiophene-3-carbonyl)-1 '-(aryl)-1 ',2 ',5 ',6 ',7 ',7a '-hexahydrospiro[indoline-3,3 '-pyrrolizin]-2-one derivatives are described here. The spirooxindole title compounds were obtained from the regio- and diastereoselective 1,3-dipolar cycloaddition reaction between an intermediate azomethine ylide and different chalcones. The structures of all compounds were proposed based on elemental analysis, ATR-FTIR, 1H NMR, 13C NMR, ESIMS, and HRESIMS. Single crystal x-ray structure determinations for some derivatives confirm the proposed structures. All synthesized compounds showed high cytotoxicity toward A549, HCT116, MCF7, DU145, and K562 but eight of them were also toxic toward normal skin fibroblast cell lines. Compound 4b showed moderate cytotoxicity toward A549 and MCF7 while 4c was highly cytotoxic toward DU145 and K562 and moderately toxic toward other cell lines. Both compounds were nontoxic toward normal skin fibroblast which makes them good drug candidates. A series of spiro[indoline-3,3 '-pyrrolizin]-2-ones containing 2,5-dichlorothiophene-3-carbonyl has been synthesized and fully characterized. Crystal structure and supramolecularity are discussed. Anti-cancer assessment shows that compounds 4b and 4c are good drug candidates.image