**4. Conclusions**

In summary, we synthesized a series of new spirooxindole analogues based on di-substituted isatin. The anticancer activity of the compounds against three different cancer cell lines was explored. Among the analogues, the compound spirooxindole analogue **5g** had an inhibitory growth potency in HCT116 similar to that of cisplatin, but it is ca. 1.8 (in HepP2) or 2.25 (in MCF7) times more potent than the reference drug, and also showed good physicochemical parameters and lipophilicity value. Further investigation of the mechanism of action of compound **5g** is required.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/2076-3417/10/6/2170/s1, characterization of the synthesized compounds; protocol for anticancer activity; ROCS protocol, Figures of the NMR spectrum.

**Author Contributions:** Conceptualization, A.B.; Data curation, F.F.E.-S., and F.A.B.; Formal analysis, F.F.E.-S., F.A.B., and A.F.M.M.R.; Funding acquisition, A.M.A.-M.; Investigation, M.S.I.; Methodology, M.S.I.; Resources, A.M.A.-M.; Supervision, Y.A.M.M.E.; Validation, A.B.; Writing—original draft, A.B. and Y.A.M.M.E.; Writing—review and editing, F.A.B., A.B., and Y.A.M.M.E. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by King Saud University, research group (No. RGP-044). **Acknowledgments:** The authors would like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for providing funding to the research group (No. RGP-044). Thanks to RSSU for their technical support. Yaseen A. M. M. Elshaier acknowledges the OpenEye scientific software for providing academic license.

**Conflicts of Interest:** The authors declare no conflict of interest.
