Synthesis and Antitumor Activity of (3-Hydroxyacrylato-O,O′) Diammineplatinum(II)

Abstract

As an indispensable part of cancer chemotherapy, platinum drugs still play an important role in cancer treatment. In this study, two platinum(II) complexes with Michael acceptor 3-hydroxyacrylic acid as the leaving group were synthesized from cis-diamminediiodo platinum(II) and 3-ethoxyacrylic acid. The structures of complexes 1 and 2 were confirmed by elemental analysis, infrared, 1H NMR, 13C NMR, and HRMS (high-resolution mass spectrometry). Results from MTT assay showed that complexes 1 and 2 significantly inhibited the growth of the four human tumor cell lines (HCT-116, A549, CFPAC-1, and BxPC-3) with the IC50 values of the two compounds similar to that of the control drug (oxaliplatin) on HCT-116 and A549. Besides, results from an in vivo study in a mouse S180 sarcoma model showed that complex 1 had a higher antitumor activity in comparison to oxaliplatin. In conclusion, our article indicated that complex 1 deserved further research and development in cancer treatment.

Cytotoxic Pt(ii) complexes containing alizarin: a selective carrier for DNA metalation

“…This series of 3-hydroxyacrylatoplatinum(II) complexes containing Michael acceptors as leaving groups afforded anticancer complexes with similar activity to oxaliplatin but with a better safety profile in vivo. 31 However, the use of O,O leaving groups different from the popular dicarboxylates for the synthesis of platinum complexes endowed with a new biological profile remains largely unexplored. In this regard, the catechol moiety in alizarin as a dichelating O,O leaving ligand in platinum complexes should represent a truly novel approach for the development of anticancer drugs with higher selectivity.…”

“…This series of 3-hydroxyacrylatoplatinum( ii ) complexes containing Michael acceptors as leaving groups afforded anticancer complexes with similar activity to oxaliplatin but with a better safety profile in vivo . 31…”