Synthesis of spiroindolone analogue via three components reaction of olefin with isatin and sarcosine: Anti-proliferative activity and computational studies

Considerable attention has been focused on the [1,3] dipolar cycloaddition reaction approach of olefin with amino acid (sarcosine), and isatin which underwent smoothly, and afforded a highly functionalized complex molecule. The target spiroindolone analogue 4 was synthesized in excellent yield. The desired compound was elucidated based on X-ray single crystal diffraction technique. Compound 4 was examined against three different cancer cell lines for liver, breast and colorectal cancer (HepG2, MCF-7 and HCT-116, respectively). It showed high selectivity against colon cancer (HCT-116). Hirshfeld molecular packing analysis of 4 showed that the H center dot center dot center dot H, Cl center dot center dot center dot H and C center dot center dot center dot H contacts are the most abundant while the N center dot center dot center dot H and O center dot center dot center dot H hydrogen bonding interactions are the strongest. Molecular and electronic structures as well as the Uv-Vis and NMR spectra of 4 were discussed based on DFT calculations. The longest wavelength band observed at 298 nm was assigned for the HOMO-2/HOMO-1 -> LUMO excitations. The H-1 and C-13 NMR chemical shifts of 4 were calculated and compared with the experimental data (0.934 -0.954). (C) 2019 Elsevier B.V. All rights reserved.