Synthesis and anti-Cancer Activity of a New Hybrid Based Spirooxindole-Pyrrolidine -Thiochromene Scaffolds via [3+2] Cycloaddition Reaction: Computational Investigation

A combined experimental and theoretical study of a newly synthesized cycloadduct of spirooxindole based thiochromene scaffold via [3 + 2] cycloaddition (32CA) reaction approach has been performed. The final adducts occurred via reaction of azomethine ylide (AY) with the ethylene derivative via ortho/endo 32CA protocol in respective regio- and diastereoselective fashion. In the light of the importance of intermolecular interactions in the crystal stability, Hirshfeld calculations were employed to predict all possible contacts affecting the molecular packing in the solid state of the studied systems. The results shed the light on the importance of O horizontal ellipsis H, F horizontal ellipsis H and H horizontal ellipsis C interactions as well as the pi-pi stacking interactions on the molecular packing. DFT calculations were used to compute the minimum energy structures and predict their electronic properties such as dipole moment, charge population and conceptual DFT reactivity descriptors. The H-1- and C-13-NMR spectra of the studied systems were calculated and the resulting chemical shifts correlated very well with the experimental data (R-2= 0.991-0.978). The anti-cancer activity of the synthesized spirooxindole based thiochromene motif was assessed and showed IC50 of 8.34 +/- 0.64, 11.25 +/- 0.28, 16.0 +/- 0.7, and 25.3 +/- 0.25 mu M against the four cancer cell lines MCF-7, MDA-MB231, PC3, and HeLa, respectively.

Automated summary

A combined experimental and theoretical study was conducted on a newly synthesized compound based on spirooxindole and thiochromene. The study revealed the importance of intermolecular interactions in crystal stability, and predicted the electronic properties and chemical shifts using computational methods. Furthermore, the compound exhibited anti-cancer activity.