Synthesis, Characterization, and Cytotoxicity of New Spirooxindoles Engrafted Furan Structural Motif as a Potential Anticancer Agent.

A new series of spirooxindoles based on ethylene derivatives having furan aryl moiety are reported. The new hybrids were achieved via [3 + 2] cycloaddition reaction as an economic one-step efficient approach. The final constructed spirooxindoles have four contiguous asymmetric carbon centers. The structure of is exclusively confirmed using X-ray single crystal diffraction. The supramolecular structure of is controlled by O···H, H···H, and C···C intermolecular contacts. It includes layered molecules interconnected weak C-H···O (2.675 Å), H···H (2.269 Å), and relatively short Cl···Br interhalogen interactions [3.4500(11)Å]. Using Hirshfeld analysis, the percentages of these intermolecular contacts are 10.6, 25.7, 6.4, and 6.2%, respectively. The spirooxindoles along with ethylene derivatives having furan aryl moiety were assessed against breast (MCF7) and liver (HepG2) cancer cell lines. The results indicated that the new chalcone showed excellent activity in both cell lines (MCF7 and HepG2) with IC = 4.1 ± 0.10 μM/mL (MCF7) and 3.5 ± 0.07 μM/mL (HepG2) compared to staurosporine with 4.3 and 2.92 folds. Spirooxindoles (IC = 4.3 ± 0.18 μM/mL), (IC = 10.3 ± 0.40 μM/mL), (IC = 10.7 ± 0.38 μM/mL), and (IC = 4.7 ± 0.18 μM/mL) exhibited potential activity against breast adenocarcinoma, while compounds (IC = 6.9 ± 0.23 μM/mL) and (IC = 3.5 ± 0.11 μM/mL) were the most active hybrids against human liver cancer cell line (HepG2) compared to staurosporine [IC = 17.8 ± 0.50 μM/mL (MCF7) and 10.3 ± 0.23 μM/mL (HepG2)]. Molecular docking study exhibited the virtual mechanism of binding of compound as a dual inhibitor of EGFR/CDK-2 proteins, and this may highlight the molecular targets for its cytotoxic activity.