Novel synthesis of palladium (II) complexes derived from 3-arylsydnone-4-carbaldehyde N(4)-phenylthiosemicarbazones and biological activity

Abstract

Objectives The aim of this research is to investigate whether the oxygen atom O(6) in the sydnone ring of 3-arylsydnone-4-carbaldehyde N(4)-phenylthiosemicarbazones (HArSYTSCs, 3a-d) is a good electron donor atom upon metal complexation. Furthermore, ligands 3a-d and the corresponding palladium complexes (Pd(ArSYTSC)Cl, 4a-d) would be expected to find their potent biological activities. Methods The desired palladium complexes 4a-d were first synthesized from thiosemicarbazones 3a-d. Then, the antiproliferative activity of ligands 3a-d and complexes 4a-d were tested against human hepatocellular carcinoma and human cervical epithelioid carcinoma (HeLa) cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl trazolium bromide (MTT) assay. Key findings According to X-ray analyses, ligands 3a-d are bonded to the Pd (II) center in an O, N, S-tridentate coordination mode through sydnone carbonyl oxygen O(6), azomethine nitrogen and the thiolate sulfur atom. The carbonyl oxygen of the sydnone ring is found to be a good electron donor site upon metal complexation. Moreover, MTT assay results reveal that the palladium complexes 4a-d have greater antiproliferative activity than 5-fluorouracil. In particular, the complexes exhibit obvious better activity than the corresponding ligands 3a-d against HeLa cell. Conclusions The results indicate that the synthesized novel palladium complexes have greater antiproliferative activity than both 5-fluorouracil and the corresponding ligands against HeLa cell. Accordingly, the study of sydnonyl complexes bearing anticancer activities may support the development of coordination chemistry. © 2013 Royal Pharmaceutical Society.