Stereoselective Synthesis of Spirooxindole Derivatives Using One-Pot Multicomponent Cycloaddition Reaction and Evaluation of Their Antiproliferative Efficacy.

Abstract

A highly stereoselective, one-pot, multicomponent method has been developed to synthesize pyrrolizidine- and N-methyl pyrrolidine-substituted spirooxindole derivatives. The [3 + 2] cycloaddition reaction involves the reaction between the dipole azomethine ylides, generated in situ from the reaction between isatin and secondary amino acids such as L-proline or sarcosine, and α,β-unsaturated carbonyl compounds as the dipolarophile. The reaction condition was optimized to achieve excellent regio- and stereoselectivity. Products were obtained in good yield using ethanol as a solvent at the reflux temperature. The newly synthesized spirooxindole derivatives were evaluated for their antiproliferative efficacy against National Cancer Institute (NCI)-60 cancer cell lines and DNA G-quadruplex (G4) interaction capacity. Compound 14b produced selective cytotoxicity against leukemia, renal, colon, and prostate cancer cell lines at a 10 μM concentration. The G4 interaction studies further suggested that these spirooxindole derivatives were devoid of any activity as DNA G4 ligands.