Synthesis and Antitumor Activity of a GSH Inert Bisphosphonate Platinum (II) Complex

Author:

Ma Lu123ORCID,Liu Hua4ORCID,Ju Yichun5ORCID,Chen Kai6ORCID,Yang Yi7ORCID,Zhou Zhichao7ORCID,Zhang Zhenqin5ORCID,Cai Zheng5ORCID

Affiliation:

1. Department of Periodontology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing 210029, China

2. Jiangsu Province Key Laboratory of Oral Diseases, Nanjing 210029, China

3. Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing 210029, China

4. School of Chemistry and Chemical Engineering, Anshun University, Anshun 561000, China

5. School of Pharmacy, Nanjing Medical University, Nanjing 211166, China

6. Collaborative Innovation Center of Atmospheric Environment and Equipment Technology, Jiangsu Key Laboratory of Atmospheric Environment Monitoring and Pollution Control, Nanjing University of Information Science & Technology, Nanjing 210044, China

7. Changzhou Vocational Institute of Engineering, Changzhou 213164, China

Abstract

Osteosarcoma is a highly aggressive neoplasm. Traditional platinum chemotherapeutic agents for osteosarcoma inevitably have acquired drug resistance and serious side effects, which have limited their utility. To slow down the reaction of platinum drugs with glutathione (GSH) is a strategy to overcome the resistance of platinum chemotherapeutic agents. Herein, the unique design of a GSH inert bisphosphonate platinum complex cis-{di(amino)platinum[tetraethyl 2,2-bis(2-pyridinylmethyl)methylidene-1,1-bisphosphonate]} (DBPP) is reported. MTT assay demonstrates that DBPP showed moderate inhibition towards human osteosarcoma cell line U2OS cells. The cytostatic action of DBPP is related to conformational conversion from B-DNA to A-DNA and the unwinding of pUC19 DNA. DBPP could also destroy the tertiary structure of human serum albumin (HSA). Notably, 31P NMR and 1H NMR indicate that DBPP can hardly chelate with GSH, which could overcome the GSH-induced side effects. We envision that this unique design of the platinum complex would open up new ways to overcome GSH-induced resistance.

Funder

Innovation and Entrepreneurship Program of College Students in Jiangsu

Publisher

Hindawi Limited

Subject

General Chemistry

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