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

Mezna Saleh Altowyan; Saied M Soliman; Matti Haukka; Nora Hamad Al-Shaalan; Aminah A Alkharboush; Assem Barakat

doi:10.1021/acsomega.2c03790

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

ACS Omega. 2022 Sep 27;7(40):35743-35754. doi: 10.1021/acsomega.2c03790. eCollection 2022 Oct 11.

Authors

Mezna Saleh Altowyan¹, Saied M Soliman², Matti Haukka³, Nora Hamad Al-Shaalan¹, Aminah A Alkharboush¹, Assem Barakat⁴

Affiliations

¹ Department of Chemistry, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
² Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia, Alexandria 21321, Egypt.
³ Department of Chemistry, University of Jyväskylä, P.O. Box 35, Jyväskylä FI-40014 Finland.
⁴ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.

Abstract

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 3a is exclusively confirmed using X-ray single crystal diffraction. The supramolecular structure of 3a 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 3b showed excellent activity in both cell lines (MCF7 and HepG2) with IC₅₀ = 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 6d (IC₅₀ = 4.3 ± 0.18 μM/mL), 6f (IC₅₀ = 10.3 ± 0.40 μM/mL), 6i (IC₅₀ = 10.7 ± 0.38 μM/mL), and 6j (IC₅₀ = 4.7 ± 0.18 μM/mL) exhibited potential activity against breast adenocarcinoma, while compounds 6d (IC₅₀ = 6.9 ± 0.23 μM/mL) and 6f (IC₅₀ = 3.5 ± 0.11 μM/mL) were the most active hybrids against human liver cancer cell line (HepG2) compared to staurosporine [IC₅₀ = 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 3b as a dual inhibitor of EGFR/CDK-2 proteins, and this may highlight the molecular targets for its cytotoxic activity.