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

Yong-Zhi Shu,Bin Zhou,Hai-Feng Hu,Quan-Hai Liu,Dian-Wen Ju,Jun Lin,Bao-Quan Zhu

doi:10.1055/s-0041-1730956

Yong-Zhi Shu, Bin Zhou + Show 5 more

Open Access

https://doi.org/10.1055/s-0041-1730956

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Abstract

AbstractAs 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.

Highlights

Cisplatin, a platinum(II) complex, has made a major impact in the chemotherapeutic treatment of testicular and ovarian cancers since the accidental discovery of its biological activity, and is widely used in the treatment of these types of cancers.[1,2] it still has nonnegligible toxic and side effects such as nephrotoxicity, emetogenicity, and drug resistance, which cripple its overall effectiveness in cancer therapy.[3,4,5,6] For decades, thousands of platinum(II) complexes have been prepared in the hope of finding those with more tolerable toxicological profile and higher efficacy.[7]
Thousands of platinum(II) complexes have been prepared in the hope of finding those with more tolerable toxicological profile and higher efficacy.[7]. These efforts have brought several new drugs into market,[8,9,10] followed by several new complexes emerging in current clinical trials (►Fig. 1).[11]
With regard to most of the platinum(II) complexes, such as carboplatin and oxaliplatin, dicarboxylate plays a role as the leaving group in the mechanism of the interaction between platinum(II) complex and DNA, and in addition to platinum(II) complexes containing dicarboxylate as the leaving group, there are platinum(II) complexes, such as nedaplatin and lobaplatin, containing α-hydroxylcarboxylate as the leaving group, which will have more stronger antitumor activity.[12]

Summary

Introduction

A platinum(II) complex, has made a major impact in the chemotherapeutic treatment of testicular and ovarian cancers since the accidental discovery of its biological activity, and is widely used in the treatment of these types of cancers.[1,2] it still has nonnegligible toxic and side effects such as nephrotoxicity, emetogenicity, and drug resistance, which cripple its overall effectiveness in cancer therapy.[3,4,5,6] For decades, thousands of platinum(II) complexes have been prepared in the hope of finding those with more tolerable toxicological profile and higher efficacy.[7]. Complexes ► antitumor activity ► Michael acceptor 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.

Results

Conclusion