Subscribe to RSS
Synthesis and Antitumor Activity of (3-Hydroxyacrylato-O,O′) Diammineplatinum(II)Funding This work was supported by the Shanghai Innovation Action Plan of Science and Technology (Grant No. 14431905900). We thank Dr. MA Jing for support.
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.
In this study, the use of mice was approved by Animal Care and Use Committee of Shanghai Institute of Pharmaceutical Industry.
Received: 02 April 2021
Accepted: 21 April 2021
25 June 2021 (online)
© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
- 1 Kelland L. The resurgence of platinum-based cancer chemotherapy. Nat Rev Cancer 2007; 7 (08) 573-584
- 2 Tchounwou PB, Dasari S, Noubissi FK, Ray P, Kumar S. Advances in our understanding of the molecular mechanisms of action of cisplatin in cancer therapy. J Exp Pharmacol 2021; 13: 303-328
- 3 Yao X, Panichpisal K, Kurtzman N, Nugent K. Cisplatin nephrotoxicity: a review. Am J Med Sci 2007; 334 (02) 115-124
- 4 Imig JD, Hye Khan MA, Burkhan A, Chen G, Adebesin AM, Falck JR. Kidney-targeted epoxyeicosatrienoic acid analog, EET-F01, reduces inflammation, oxidative stress, and cisplatin-induced nephrotoxicity. Int J Mol Sci 2021; 22 (06) 2793
- 5 Navari RM, Ruddy KJ, LeBlanc TW. et al. Avoidable acute care use associated with nausea and vomiting among patients receiving highly emetogenic chemotherapy or oxaliplatin. Oncologist 2021; 26 (04) 325-331
- 6 Zhao J, Tan W, Zhang L. et al. FGFR3 phosphorylates EGFR to promote cisplatin-resistance in ovarian cancer. Biochem Pharmacol 2021; (e-pub ahead of print) DOI: 10.1016/j.bcp.2021.114536.
- 7 Jin S, Guo Y, Guo Z, Wang X. Monofunctional platinum(II) anticancer agents. Pharmaceuticals (Basel) 2021; 14 (02) 133
- 8 Zhou J, Kang Y, Chen L. et al. The drug-resistance mechanisms of five platinum-based antitumor agents. Front Pharmacol 2020; 11: 343
- 9 Dilruba S, Kalayda GV. Platinum-based drugs: past, present and future. Cancer Chemother Pharmacol 2016; 77 (06) 1103-1124
- 10 Akshintala S, Marcus L, Warren KE. et al. Phase 1 trial and pharmacokinetic study of the oral platinum analog satraplatin in children and young adults with refractory solid tumors including brain tumors. Pediatr Blood Cancer 2015; 62 (04) 603-610
- 11 Wang X, Guo Z. Targeting and delivery of platinum-based anticancer drugs. Chem Soc Rev 2013; 42 (01) 202-224
- 12 Ye QS, Lou LG, Liu WP. et al. Synthesis and in vitro cytotoxicity of novel lipophilic (diamine)platinum(II) complexes of salicylate derivatives. Bioorg Med Chem Lett 2007; 17 (08) 2146-2149
- 13 Zhao QS, Cong YW. Michael reaction acceptor molecules in chemical biology. Huaxue Jinzhan 2007; 19 (12) 1972-1976
- 14 Wijeratne EM, Bashyal BP, Liu MX. et al. Geopyxins A-E, ent-kaurane diterpenoids from endolichenic fungal strains Geopyxis aff. majalis and Geopyxis sp. AZ0066: structure-activity relationships of geopyxins and their analogues. J Nat Prod 2012; 75 (03) 361-369
- 15 Santagata S, Xu YM, Wijeratne EM. et al. Using the heat-shock response to discover anticancer compounds that target protein homeostasis. ACS Chem Biol 2012; 7 (02) 340-349
- 16 Wang J, Yun D, Yao J. et al. Design, synthesis and QSAR study of novel isatin analogues inspired Michael acceptor as potential anticancer compounds. Eur J Med Chem 2018; 144: 493-503
- 17 Silva H, Barra CV, Rocha FV, Frezard F, Lopes MTP, Fontes APS. Novel platinum(II) complexes of long chain aliphatic diamine ligands with oxalato as the leaving group: comparative cytotoxic activity relative to chloride precursors. J Braz Chem Soc 2010; 21 (10) 1961-1967
- 18 Park DG. Antichemosensitizing effect of resveratrol in cotreatment with oxaliplatin in HCT116 colon cancer cell. Ann Surg Treat Res 2014; 86 (02) 68-75
- 19 Liu W, Chen X, Xie M. et al. Synthesis and anticancer activity of [2-hydroxy-1,3-diaminopropane-kappa 2N,N′] platinum(II) complexes. J Inorg Biochem 2008; 102 (10) 1942-1946