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Synthesis of novel spirooxindole-pyrrolidines and evaluation of their cytotoxic activity.


A variety of spirooxindoles have demonstrated cytotoxic activity toward several cancer cell lines. This study investigates the cytotoxicity of five novel spirooxindole-pyrrolidines by using the Vero and HeLa cell lines. Vero and HeLa cells were treated with the synthesized spirooxindoles, and the cytotoxicity was evaluated by using the AlamarBlue Cell Viability Reagent and live/dead assay. A series of poly-substituted pyrrolidines differing in nature and in substituent positions were obtained, with yields of 42-63%. Of the synthesized cycloadducts, 3-picolinoyl-4-(2,4-dichlorophenyl)-5-phenylspiro[indoline-3,2'-pyrrolidine]-2'-one (4) was the most cytotoxic (IC < 20 μg/ml for both cell lines). Besides, 3-picolinoyl-4-(2-chlorophenyl)-5-phenylspiro[indoline-3,2'-pyrrolidine]-2'-one (1) was three times more toxic to the HeLa cancer cell line (IC = 70 μg/ml) than it was to the Vero healthy cell line. The cytotoxicity of compounds 1 and 4 was confirmed with a live/dead assay. The cytotoxicity of a molecule was found to depend on the substitution nature on the benzene ring at the C-4 atom. 3-Picolinoyl-4-(2-chlorophenyl)-5-phenylspiro[indoline-3,2'-pyrrolidine]-2'-one (1) can be used as a source for the synthesis of novel therapeutic agents against cancer. Copyright © 2018 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.