Investigations of the Kinetics and Mechanism of Reduction of a Carboplatin Pt(IV) Prodrug by the Major Small-Molecule Reductants in Human Plasma
Abstract
:1. Introduction
2. Experimental
2.1. Reagents and Solutions
2.2. Measurements of Kinetic Data
2.3. Product Analysis
3. Results and Discussion
3.1. Reduction of [Pt(cdbca)(NH3)2Cl2] by Biothiols
3.2. Reduction of [Pt(cdbca)(NH3)2Cl2] by Ascorbate
3.3. Rate Comparison and Biological Implications
3.4. Reactivity of the Cys and GSH Species in the Reduction of cis,trans-[Pt(cbdca)(NH3)2Cl2]
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
- Hanif, M.; Hartinger, C.G. Anticancer metallodrugs: Where is the next cisplatin. Future Med. Chem. 2018, 10, 615–617. [Google Scholar] [CrossRef] [PubMed]
- Kenny, R.G.; Marmion, C.J. Toward multi-targeted platinum and ruthenium drugs—A new paradigm in cancer drug treatment regimens. Chem. Rev. 2019, 119, 1058–1137. [Google Scholar] [CrossRef] [PubMed]
- Wheate, N.J.; Walker, S.; Craig, G.E.; Oun, R. The status of platinum anticancer drugs in clinic and clinical trials. Dalton Trans. 2010, 39, 8113–8127. [Google Scholar] [CrossRef] [PubMed]
- Montaña, Á.M.; Batalla, C. The rational design of anticancer platinum complexes: The importance of the structure-activity relationship. Curr. Med. Chem. 2009, 16, 2235–2260. [Google Scholar] [CrossRef] [PubMed]
- Qun, R.; Moussa, Y.E.; Wheate, N.J. The side effects of platinum-based chemotherapy drugs: A review for chemists. Dalton Trans. 2018, 47, 6645–6653. [Google Scholar]
- Doshi, G.; Sonpavde, G.; Sternberg, C.N. Clinical and pharmacokinetic evaluation of satraplatin. Expert Opin. Drug Metab. Toxicol. 2012, 8, 103–111. [Google Scholar] [CrossRef] [PubMed]
- Brock, P.R.; Knight, K.P.; Freyer, D.R.; Campbell, K.C.M.; Steyger, P.S.; Blakley, B.W.; Rassekh, S.R.; Chang, K.W.; Fligor, B.J.; Reajput, K.; et al. Platinum-induced ototoxicity in children: A consensus review on mechanisms, predisposition, and protection, including a new international society of pediatric oncology Boston ototoxicity scale. J. Clin. Oncol. 2012, 30, 2408–2417. [Google Scholar] [PubMed]
- Sar, D.G.; Montes-Bayon, M.; Gonzalez, E.B.; Zapico, L.M.S.; Sanz-Medel, A. Reduction of cisplatin-induced nephrotoxicity in vivo by selenomethionine: The effect on cisplatin–DNA adducts. Chem. Res. Toxicol. 2011, 24, 896–904. [Google Scholar]
- Najjar, A.; Rajabi, N.; Karaman, R. Recent approaches to the platinum(IV) prodrugs: A variety of strategies for enhanced delivery and efficacy. Curr. Pharm. Design 2017, 23, 2366–2376. [Google Scholar] [CrossRef] [PubMed]
- Kenny, R.G.; Chuah, S.W.; Crawford, A.; Marmion, C.J. Platinum(IV) prodrugs-a step closer to Ehrlich’s vision. Eur. J. Inorg. Chem. 2017, 1596–1612. [Google Scholar] [CrossRef]
- Xiao, H.; Yan, L.; Dempsey, E.M.; Song, W.; Qi, R.; Li, W.; Huang, Y.; Jing, X.; Zhou, D.; Ding, J.; et al. Recent progress in polymer-based drug delivery systems. Prog. Polym. Sci. 2018, 87, 70–106. [Google Scholar] [CrossRef]
- Pathak, R.K.; Dhar, S. Unique use of alkylation for chemo-redox activity by a PtIV prodrug. Chem. Eur. J. 2016, 22, 3029–3036. [Google Scholar] [CrossRef] [PubMed]
- Petruzzella, E.; Sirota, R.; Solazzo, I.; Gandin, V.; Gibson, D. Triple action Pt(IV) derivatives of cisplatin: A new class of potent anticancer agents that overcome resistance. Chem. Sci. 2018, 9, 4299–4307. [Google Scholar] [CrossRef] [PubMed]
- Yap, S.Q.; Chin, C.F.; Thng, A.H.H.; Pang, Y.Y.; Ho, H.K.; Ang, W.H. Finely tuned asymmetric platinum(IV) anticancer complexes: Structure–Activity relationship and application as orally available prodrugs. ChemMedChem 2017, 12, 300–311. [Google Scholar] [CrossRef] [PubMed]
- Ma, Z.Y.; Wang, D.B.; Song, X.Q.; Wu, Y.G.; Chen, Q.; Zhao, C.L.; Li, J.Y.; Cheng, S.H.; Xu, J.Y. Chlorambucil-conjugated platinum(IV) prodrugs to treat triple-negative breast cancer in vitro and in vivo. Eur. J. Med. Chem. 2018, 157, 1292–1299. [Google Scholar] [CrossRef] [PubMed]
- Chen, H.; Chen, F.; Hu, W.; Gou, S. Effective platinum(IV) prodrugs conjugated with lonidamine as a functional group working on the mitochondria. J. Inorg. Biochem. 2018, 180, 119–128. [Google Scholar] [CrossRef] [PubMed]
- Xu, Z.; Li, C.; Tong, Z.; Ma, L.; Tse, M.K.; Zhu, G. Halogenated PtIV complexes from N-halosuccinimide oxidation of PtII antitumor drugs: Synthesis, mechanistic investigation, and cytotoxicity. Eur. J. Inorg Chem. 2017, 1706–1712. [Google Scholar] [CrossRef]
- Johnstone, T.C.; Alexander, S.M.; Wilson, J.J.; Lippard, S.J. Oxidative halogenation of cisplatin and carboplatin: Synthesis, spectroscopy, and crystal and molecular structures of Pt(IV) prodrugs. Dalton Trans. 2015, 44, 119–129. [Google Scholar] [CrossRef] [PubMed]
- Ma, J.; Wang, Q.; Huang, Z.; Yang, X.; Nie, G.; Hao, W.; Wang, P.G.; Wang, X. Glycosylated platinum(IV) complexes as substrates for glucose transporters (GLUTs) and organic cation transporters (OCTs) exhibited cancer targeting and human serum albumin binding properties for drug delivery. J. Med. Chem. 2017, 60, 5736–5748. [Google Scholar] [CrossRef] [PubMed]
- Hu, W.; Zhao, J.; Hua, W.; Gou, S. A study on platinum(IV) species containing an estrogen receptor modulator to reverse tamoxifen resistance of breast cancer. Metallomics 2018, 10, 346–359. [Google Scholar] [CrossRef] [PubMed]
- Mitra, K. Platinum complexes as light promoted anticancer agents: A redefined strategy for controlled activation. Dalton Trans. 2016, 45, 19157–19171. [Google Scholar] [CrossRef] [PubMed]
- Turell, L.; Radi, R.; Alvarez, B. The thiol pool in human plasma: The central contribution of albumin to redox processes. Free Radic. Biol. Med. 2013, 65, 244–253. [Google Scholar] [CrossRef] [PubMed]
- Dong, J.; Ren, Y.; Huo, S.; Shen, S.; Xu, J.; Tian, H.; Shi, T. Reduction of ormaplatin and cis-diamminetetrachloroplatinum(IV) by ascorbic acid and dominant thiols in human plasma: Kinetic and mechanistic analyses. Dalton Trans. 2016, 45, 11326–11337. [Google Scholar] [CrossRef] [PubMed]
- Carr, J.L.; Tingle, M.D.; McKeage, M.J. Satraplatin activation by haemoglobin, cytochrome c and liver microsomes in vitro. Cancer Chemother. Pharmacol. 2006, 57, 483–490. [Google Scholar] [CrossRef] [PubMed]
- Nemirovski, A.; Kasherman, Y.; Tzaraf, Y.; Gibson, D. Reduction of cis,trans,cis-[PtCl2(OCOCH3)2(NH3)2] by aqueous extracts of cancer cells. J. Med. Chem. 2007, 50, 554–556. [Google Scholar] [CrossRef] [PubMed]
- Lasorsa, A.; Stachlikova, O.; Brabec, V.; Natile, G.; Arnesano, F. Activation of platinum(IV) prodrugs by cytochrome c and characterization of the protein binding sites. Mol. Pharm. 2016, 13, 3216–3223. [Google Scholar] [CrossRef] [PubMed]
- Mayr, J.; Heffeter, P.; Groza, D.; Galvez, L.; Koellensperger, G.; Roller, A.; Alte, B.; Haider, M.; Berger, W.; Kowol, C.R.; et al. An albumin-based tumor-targeted oxaliplatin prodrug with distinctly improved anticancer activity in vivo. Chem. Sci. 2017, 8, 2241–2250. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Theiner, S.; Grabarics, M.; Galvez, L.; Varbanov, H.P.; Sommerfeld, N.S.; Galanski, M.; Keppler, B.K.; Koellensperger, G. The impact of whole human blood on the kinetic inertness of platinum(IV) prodrugs—An HPLC-ICP-MS study. Dalton Trans. 2018, 47, 5252–5258. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Frensemeier, L.M.; Mayr, J.; Koellensperger, G.; Keppler, B.K.; Kowol, C.R.; Karst, U. Structure elucidation and quantification of the reduction products of anticancer Pt(IV) prodrugs by electrochemistry/mass spectrometry (EC-MS). Analyst 2018, 143, 1997–2001. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hall, M.D.; Daly, H.L.; Zhang, J.Z.; Zhang, M.; Alderden, R.A.; Pursche, D.; Foran, G.J.; Hambley, T.W. Quantitative measurement of the reduction of platinum(IV) complexes using X-ray absorption near-edge spectroscopy (XANES). Metallomics 2012, 4, 568–575. [Google Scholar] [CrossRef] [PubMed]
- Chen, C.K.J.; Kappen, P.; Hambley, T.W. The reduction of cis-platinum(IV) complexes by ascorbate and in whole human blood models using 1H NMR and XANES spectroscopy. Metallomics 2019, 11, 686–695. [Google Scholar] [CrossRef] [PubMed]
- Chipman, A.; Yates, B.F.; Canty, A.; Ariafared, A. Reduction of a platinum(IV) prodrug model by sulfur containing biological reductants: Computational mechanistic elucidation. Chem. Commun. 2018, 54, 10491–10494. [Google Scholar] [CrossRef] [PubMed]
- Šebesta, F.; Baxová, K.; Burda, J.V. Redox potentials for tetraplatin, satraplatin, its derivatives, and ascorbic acid: A computational study. Inorg. Chem. 2018, 57, 951–962. [Google Scholar] [CrossRef] [PubMed]
- Dabbish, E.; Ponte, F.; Russo, N.; Sicilia, E. Antitumor platinium(IV) prodrugs: A systematic computational exploration of their reduction mechanism by l-ascorbic acid. Inorg. Chem. 2019, 58, 3851–3860. [Google Scholar] [CrossRef] [PubMed]
- Lorenzo, J.; Montaña, Á.M. The molecular shape and the field similarities as criteria to interpret SAR studies for fragment-based design of platinum(IV) anticancer agents. Correlation of physicochemical properties with cytotoxicity. J. Mol. Graph. Model 2016, 69, 39–60. [Google Scholar] [CrossRef] [PubMed]
- Tian, H.; Dong, J.; Chi, X.; Xu, L.; Shi, H.; Shi, T. Reduction of cisplatin and carboplatin Pt(IV) prodrugs by homocysteine: Kinetic and mechanistic investigations. Int. J. Chem. Kinet. 2017, 49, 681–689. [Google Scholar] [CrossRef]
- Dong, J.; Tian, H.; Song, C.; Shi, T.; Elding, L.I. Reduction of ormaplatin by an extended series of thiols unravels a remarkable correlation. Dalton Trans. 2018, 47, 5548–5552. [Google Scholar] [CrossRef] [PubMed]
- Dong, J.; Ren, Y.; Sun, S.; Yang, J.; Nan, C.; Shi, H.; Xu, J.; Duan, J.; Shi, T.; Elding, L.I. Kinetics and mechanism for oxidation of the anti-tubercular prodrug isoniazid and its analog by iridium(IV) as models for biological redox systems. Dalton Trans. 2017, 46, 8377–8386. [Google Scholar] [CrossRef] [PubMed]
- Liu, C.; Xu, L.; Tian, H.; Yao, H.; Elding, L.I.; Shi, T. Kinetics and mechanism for reduction of anticancer model compounds by Se-methyl L-selenocysteine. Comparison with L-selenomethionine. J. Mol. Liq. 2018, 271, 838–843. [Google Scholar] [CrossRef] [Green Version]
- Wang, Y.N.; Lau, K.C.; Lam, W.W.Y.; Man, W.L.; Lau, T.C. Kinetics and mechanism of the oxidation of ascorbic acid in aqueous solutions by a trans-dioxoruthenium(VI) complex. Inorg. Chem. 2009, 48, 400–406. [Google Scholar] [CrossRef] [PubMed]
- Wilkins, P.C.; Johnson, M.D.; Holder, A.A.; Crans, D.C. Reduction of vanadium(V) by L-ascorbic acid at low and neutral pH: Kinetic, mechanistic, and spectroscopic characterization. Inorg. Chem. 2006, 45, 1471–1479. [Google Scholar] [CrossRef] [PubMed]
- Sanzenbacher, R.; Elias, H. Kinetics and mechanism of incorporation of nickel(II) into N4 macrocycles of the cyclam type: How many steps and intermediates are involved? Inorg. Chim. Acta 1996, 246, 267–274. [Google Scholar] [CrossRef]
- Wilson, R.J.; Beezer, A.E.; Mitchell, I.C. A kinetic study of the oxidation of L-ascorbic acid (vitamin C) in solution using an isothermal microcalorimeter. Thermochim. Acta 1995, 264, 27–40. [Google Scholar] [CrossRef]
- Wechtersbach, L.; Cigic, B. Reduction of dehydroascorbic acid at low pH. J. Biochem. Biophys. Methods 2007, 70, 767–772. [Google Scholar] [CrossRef] [PubMed]
- Weaver, E.L.; Bose, R.N. Platinum(II) catalysis and radical intervention in reductions of platinum(IV) antitumor drugs by ascorbic acid. J. Inorg. Biochem. 2003, 95, 231–239. [Google Scholar] [CrossRef]
- Zhang, J.Z.; Wexselblatt, E.; Hambley, T.W.; Gibson, D. Pt(IV) analogs of oxaliplatin that do not follow the expected correlation between electrochemical reduction potential and rate of reduction by ascorbate. Chem. Commun. 2012, 48, 847–849. [Google Scholar] [CrossRef] [PubMed]
- Pichler, V.; Goschl, S.; Schreiber-Brynzak, E.; Jakupec, M.A.; Galanski, M.; Keppler, B.K. Influence of reducing agents on the cytotoxic activity of platinum(IV) complexes: Induction of G2/M arrest, apoptosis and oxidative stress in A2780 and cisplatin resistant A2780cis cell lines. Metallomics 2015, 7, 1078–1090. [Google Scholar] [CrossRef] [PubMed]
- Robitaille, L.; Hoffer, L.J. A simple method for plasma total vitamin C analysis suitable for routine clinical laboratory use. Nutr. J. 2016, 15, 40. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dong, J.; Huo, S.; Shen, S.; Xu, J.; Shi, T.; Elding, L.I. Reactivity of the glutathione species towards the reduction of ormaplatin (or tetraplatin). Bioorg. Med. Chem. Lett. 2016, 26, 4261–4266. [Google Scholar] [CrossRef] [PubMed]
- Mason, W.R. Platinum(II)-catalyzed substitutions of platinum(IV) complexes. Coord. Chem. Rev. 1972, 7, 241–255. [Google Scholar] [CrossRef]
- Elding, L.I.; Gustafson, L. A reaction mechanism for oxidative addition of halogen to platinum(II), reductive elimination of halide from platinum(IV) and halide assisted anations of platinum(IV) complexes. Inorg. Chim. Acta 1976, 19, 165–171. [Google Scholar] [CrossRef]
- Wilmarth, W.K.; Dooly, R.; Byrd, J.E. The Pt(CN)4(OH)Br2− oxidation of S2O32− and S4O62−. Coord. Chem. Rev. 1983, 51, 125–140. [Google Scholar] [CrossRef]
- Sinisi, M.; Intini, F.P.; Natile, G. Dependence of the reduction products of platinum(IV) prodrugs upon the configuration of the substrate, bulk of the carrier ligands, and nature of the reducing agent. Inorg. Chem. 2012, 51, 9694–9704. [Google Scholar] [CrossRef] [PubMed]
- Smith, R.M.; Martell, A.E. Critical Stability Constants; 2nd Supplement; Plenum Press: New York, NY, USA, 1989; p. 20. [Google Scholar]
- Huo, S.; Dong, J.; Song, C.; Xu, J.; Shen, S.; Ren, Y.; Shi, T. Characterization of the reaction products, kinetics and mechanism of oxidation of the drug captopril by platinum(IV) complexes. RSC Adv. 2014, 4, 7402–7409. [Google Scholar] [CrossRef]
- Povse, V.G.; Olabe, J.A. Kinetics and mechanism of ligand interchange in the [RuIII(edta)L] complexes; L=Cysteine and related thiolates. Transit. Metal Chem. 1998, 23, 657–662. [Google Scholar] [CrossRef]
Reductant | k′/M−1s−1 (25.0 °C) | k′/M−1s−1 (37.0 °C) | kobsd/s−1 (37.0 °C) a | t½/s (37.0 °C) a |
---|---|---|---|---|
Cys | (1.93 ± 0.06) × 104 | (4.7 ± 0.2) × 104 | 0.39–0.48 | 1.8–1.4 |
GSH | (1.01 ± 0.03) × 104 | (2.65 ± 0.09) × 104 | 0.053–0.135 | 15–5 |
Hcy | (6.3 ± 0.2) × 103 | (1.70 ± 0.08) × 104 | 0.0029–0.0054 | 240–127 |
Cys–Gly | (8.2 ± 0.2) × 103 | (1.57 ± 0.05) × 104 | 0.031–0.046 | 22–15 |
Asc | (1.03 ± 0.04) × 103 | (2.2 ± 0.2) × 103 | 0.0088–0.33 | 79–2.1 |
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Liu, Y.; Tian, H.; Xu, L.; Zhou, L.; Wang, J.; Xu, B.; Liu, C.; Elding, L.I.; Shi, T. Investigations of the Kinetics and Mechanism of Reduction of a Carboplatin Pt(IV) Prodrug by the Major Small-Molecule Reductants in Human Plasma. Int. J. Mol. Sci. 2019, 20, 5660. https://doi.org/10.3390/ijms20225660
Liu Y, Tian H, Xu L, Zhou L, Wang J, Xu B, Liu C, Elding LI, Shi T. Investigations of the Kinetics and Mechanism of Reduction of a Carboplatin Pt(IV) Prodrug by the Major Small-Molecule Reductants in Human Plasma. International Journal of Molecular Sciences. 2019; 20(22):5660. https://doi.org/10.3390/ijms20225660
Chicago/Turabian StyleLiu, Yang, Hongwu Tian, Liyao Xu, Li Zhou, Jinhu Wang, Benyan Xu, Chunli Liu, Lars I. Elding, and Tiesheng Shi. 2019. "Investigations of the Kinetics and Mechanism of Reduction of a Carboplatin Pt(IV) Prodrug by the Major Small-Molecule Reductants in Human Plasma" International Journal of Molecular Sciences 20, no. 22: 5660. https://doi.org/10.3390/ijms20225660