Platinum-based
chemotherapeutic drugs such as cisplatin, carboplatin and oxaliplatin are
widely applied for the treatment of various types of tumors. However, poor
solubility, serious side effects, and more importantly, the intrinsic and
acquired resistance limit their clinical applications. These factors motivate
scientists to design and synthesize novel and more potent analogues lacking
disadvantages of clinical platinum drugs. Platinum (IV) complexes are one of
representatives. In this review, we summarized the investigations undertaken
into Platinum (IV) antitumor compounds since Rosenberg first noted their
antitumor activity. The synthesis method and mechanism of action of Platinum
(IV) complexes are outlined, as well as their chemical and pharmacological
properties. Recent advances in Platinum (IV) anticancer agents that have been
in clinical trials and photoactivatable Platinum (IV) complexes are also
summarized, and the purpose here is to provide insight into the requirements
for the antitumor activity of Platinum (IV) complexes and a basis for
progressing in a new platinum compound.
References
[1]
Jemal, A., Bray, F. and Ferlay, J. (2011) Global Cancer Statistics. CA: A Cancer Journal for Clinicians, 61, 69-90. https://doi.org/10.3322/caac.20107
[2]
Harper, B.W., Krause-Heuer, A.M., Grant, M.P., Manohar, M., Garbutcheon-Singh, K.B. and Aldrich-Wright, J.R. (2010) Advances in Platinum Chemotherapeutics. Chemistry—A European Journal, 16, 7064-7077. https://doi.org/10.1002/chem.201000148
[3]
Rosenberg, B., Camp, L.V. and Krigas, T. (1965) Inhibition of Cell Division in Escherichia coli by Electrolysis Products from a Platinum Electrode. Nature (London), 205, 698. https://doi.org/10.1038/205698a0
[4]
Kelland, L. (2007) The Resurgence of Platinum-Based Cancer Chemotherapy. Nature Reviews Cancer, 7, 573-584. https://doi.org/10.1038/nrc2167
[5]
Horwich, A., Shipley, J. and Huddart, R. (2006) Testicular Germ-Cell Cancer. Lancet, 367, 754-765. https://doi.org/10.1016/S0140-6736(06)68305-0
[6]
Dahr, S., Kolishetti, N., Lippard, S.J. and Farokhzad, O.C. (2011) Targeted Delivery of a Cisplatin Prodrug for Safer and More Effective Prostate Cancer Therapy in Vivo. Proceedings of the National Academy of Sciences of the United States of America, 108, 1850-1855. https://doi.org/10.1073/pnas.1011379108
[7]
Olszewski, U. and Hamilton, G. (2010) A Better Platinum-Based Anticancer Drug Yet to Come? Journal of Medicinal Chemistry, 10, 293-301.
[8]
Shen, D.W., Pouliot, L.M., Hall, M.D. and Gottesman, M.M. (2012) Cisplatin Resistance: A Cellular Self-Defense Mechanism Resulting from Multiple Epigenetic and Genetic Changes. Pharmacological Reviews, 64, 706-721. https://doi.org/10.1124/pr.111.005637
[9]
Urien, S., Brain, E., Bugat, R., Pivot, X., Lochon, I., Van, M.L., Vauzelle, F. and Lokiec, F. (2005) Pharmacokinetics of Platinum after Oral or Intravenous Cisplatin: A Phase 1 Study in 32 Adult Patients. Cancer Chemotherapy and Pharmacology, 55 55-60. https://doi.org/10.1007/s00280-004-0852-8
[10]
Johnstone, T.C., Suntharalingam, K. and Lippard, S.J. (2016) The Next Generation of Platinum Drugs: Targeted Pt(II) Agents, Nanoparticle Delivery, and Pt(IV) Prodrugs. Chemical Reviews, 116, 3436-3486. https://doi.org/10.1021/acs.chemrev.5b00597
[11]
Hall, M.D., Mellor, H.R., Callaghan, R., et al. (2007) Basis for Design and Development of Platinum(IV) Anticancer Complexes. Journal of Medicinal Chemistry, 50, 3403-3411. https://doi.org/10.1021/jm070280u
[12]
Giandomenico, C.M., Abrams, M.J., Murrer, B.A., Vollano, J.F., Rheinheimer, M.I., Wyer, S.B., Bossard, G.E., and Higgins, J.D. (1995) Carboxylation of Kinetically Inert Platinum(IV) Hydroxy Complexes. An Entr.acte.ee into Orally Active Platinum(IV) Antitumor Agents. Inorganic Chemistry, 34, 1015-1021. https://doi.org/10.1021/ic00109a004
[13]
Min, Y., Mao, C., Xu, D., Wang, J. and Liu, Y. (2010) Gold Nanorods for Platinum Based Prodrug Delivery. Chemical Communications, 46, 8424-8426. https://doi.org/10.1039/c0cc03108a
[14]
Wong, E. and Giandornenico, C.M. (1999) Current Status of Platinum-Based Antitumor Drugs. Chemical Reviews, 99, 2451-2466. https://doi.org/10.1021/cr980420v
[15]
Cohen, S.M. and Lippard, S.J. (2001) Cisplatin: From DNA Damage to Cancer Chemotherapy. Progress in Nucleic Acid Research and Molecular Biology, 67, 93-130.
[16]
Siddik, Z.H. (2003) Cisplatin: Mode of Cytotoxic Action and Molecular Basis of Resistance. Oncogene, 22, 7265-7279. https://doi.org/10.1038/sj.onc.1206933
[17]
Fuertes, M.A., Alonso, C. and Perez, J.M. (2003) Biochemical Modulation of Cisplatin Mechanisms of Action: Enhancement of Antitumor Activity and Circumvention of Drug Resistance. Chemical Reviews, 103, 645-662. https://doi.org/10.1021/cr020010d
[18]
Braddock, P.D., Connors, T.A., Jones, M., Khokhar, A.R., Melzack, D.H. and Tobe, M.L. (1975) Structure and Activity Relationships of Platinum Complexes with Anti-Tumour Activity. Chemico-Biological Interactions, 11, 145-161.
[19]
Prestayko, A.W., Bradner, W.T., Huftalen, J.B., Rose, W.C., Schurig, J.E., Cleare, M.J., Hydes, P.C. and Crooke, S.T. (1979) Antileukemia (L1210) Activity and Toxicity of cis-dichlorodiammineplatinum(II) Analogs. Cancer Treatment Reports, 63, 1503-1508.
[20]
Turell, L., Radi, R. and Alvarez, B. (2013) The Thiol Pool in Human Plasma: The Central Contribution of Albumin to Redox Processes. Free Radical Biology and Medicine, 65, 244-253. https://doi.org/10.1016/j.freeradbiomed.2013.05.050
[21]
Rieter, W.J., Pott, K.M., Taylor, K.M.L. and Lin, W. (2008) Nanoscale Coordination Polymers for Platinum-Based Anticancer Drug Delivery. Journal of the American Chemical Society, 130, 11584-11585. https://doi.org/10.1021/ja803383k
[22]
Roat, R.M. and Reedijk, J. (1993) Reaction of mer-Trichloro (Diethylenetriamine)Platmum(IV) Chloride, (mer-[Pt(dien)Cl3]Cl), with Purine Nucleosides and Nucleotides Results in Formation of Platinum(II) as Well as Platinum(IV) Complexes. Journal of Inorganic Biochemistry, 52, 263-274. https://doi.org/10.1016/0162-0134(93)80030-D
[23]
Dhar, S.J., Daniel, W.L., Giljohann, D.A., Mirkin, C.A. and Lippard, S.J. (2009) Polyvalent Oligonucleotide Gold Nanoparticle Conjugates as Delivery Vehicles for Platinum(IV) Warheads. Journal of the American Chemical Society, 131, 14652-14653. https://doi.org/10.1021/ja9071282
[24]
Vrana, O., Brabec, V. and Kleinwachter, V. (1986) Polarographic Studies on the Conformation of Some Platinum Complexes: Relations to Anti-Tumour Activity. Anti-Cancer Drug Design, 1, 95-109.
[25]
Choi, S., Delaney, S., Orbai, L., Padgett, E.J. and Hakemian, A.S. (2001) A platinum(IV) Complex Oxidizes Guanine to 8-oxo-guanine in DNA and RNA. Inorganic Chemistry, 40, 5481-5482..
[26]
Gibson, D. (2009) The Mechanism of Action of Platinum Anticancer Agents—What Do We Really Know about It? Dalton Transactions, No. 48, 10681-10689. https://doi.org/10.1039/b918871c
[27]
Hall, M.D. and Hambley, T.W. (2002) Platinum(IV) Antitumour Compounds: Their Bioinorganic Chemistry. Coordination Chemistry Reviews, 232, 49-67. https://doi.org/10.1016/S0010-8545(02)00026-7
[28]
Hambley, T.W., Battle, A.R., Deacon, G.B., Lawrenz, E.T., Fallon, G.D., Gatehouse, B.M., Webster, L.K. and Rainone, S. (1999) Modifying the Properties of Platinum(IV) Complexes in Order to Increase Biological Effectiveness. Journal of Inorganic Biochemistry, 77, 3-12. https://doi.org/10.1016/S0162-0134(99)00133-6
[29]
Galanski, M., Jakupec, M.A. and Keppler, B.K. (2005) Update of the Preclinical Situation of Anticancer Platinum Complexes: Novel Design Strategies and Innovative Analytical Approaches. Current Medicinal Chemistry, 12, 2075-2094. https://doi.org/10.2174/0929867054637626
[30]
Hall, M.D., Amjadi, S., Zhang, M., Beale, P.J. and Hambley, T.W. (2004) The Mechanism of Action of Platinum(IV) Complexes in Ovarian Cancer Cell Lines. Journal of Inorganic Biochemistry, 98, 1614-1624. https://doi.org/10.1016/j.jinorgbio.2004.05.017
[31]
Choi, S., Filotto, C., Bisanzo, M., Delaney, S., Lagasee, D., Whitworth, J.L., Jusko, A., Li, C.R., Wood, N.A., Willingham, J., Schwenker, A. and Spaulding, K. (1998) Reduction and Anticancer Activity of Platinum(IV) Complexes. Inorganic Chemistry, 37, 2500-2504. https://doi.org/10.1021/ic971047x
[32]
Giandomenico, C.M., Abrams, M.J., Murrer, B.A., Vollano, J.F., Rheinheimer, M.I., Wyer, S.B., Bossard, G.E. and Higgins, J.D. (1995) Carboxylation of Kinetically Inert Platinum(IV) Hydroxy Complexes. An Entr.acte.ee into Orally Active Platinum(IV) Antitumor Agents. Inorganic Chemistry, 34, 1015-1021. https://doi.org/10.1021/ic00109a004
[33]
Rodriguez-Nieto, S. and Zhivotovsky, B. (2006) Role of Alterations in the Apoptotic Machinery in Sensitivity of Cancer Cells to Treatment. Current Pharmaceutical Design, 12, 4411-4425. https://doi.org/10.2174/138161206779010495
[34]
Kelland, L.R., Abel, G., McKeage, M.J., Jones, M., Goddard, P.M., Valenti, M., Murrer, B.A. and Harrap, K.R. (1993) Preclinical Antitumor Evaluation of Bis-Acetato-Ammine-Dichloro-Cyclohexylamine Platinum(IV): An Orally Active Platinum Drug. Cancer Research, 53, 2581-2586.
[35]
Sharp, S.Y., Rogers, P.M. and Kelland, L.R. (1995) Transport of Cisplatin and Bis-Acetato-Ammine-Dichlorocyclohexylamine Platinum(IV) (JM216) in Human Ovarian Carcinoma Cell Lines: Identification of a Plasma Membrane Protein Associated with Cisplatin Resistance. Clinical Cancer Research, 1, 981-989.
[36]
Zanellato, I., Bonarrigo, I., Colangelo, D., Gabano, E., Ravera, M., Alessio, M. and Osella, D. (2014) Biological Activity of a Series of Cisplatin-Based Aliphatic Bis(Carboxylato) Pt(IV) Prodrugs: How Long the Organic Chain Should Be? Journal of Inorganic Biochemistry, 140, 219-227. https://doi.org/10.1016/j.jinorgbio.2014.07.018
[37]
Kostova, I. (2006) Platinum Complexes as Anticancer Agents. Recent Patents on Anti-Cancer Drug Discovery, 1, 1-22.
[38]
Sebesta, F. and Burda, J.V. (2016) Reduction Process of Tetraplatin in the Presence of Deoxyguanosine Monophosphate (dGMP): A Computational DFT Study. Chemistry: A European Journal, 22, 1037-1047. https://doi.org/10.1002/chem.201503555
[39]
Kipouros, I., Fica-Contreras, S.M., Bowe, G.J.K. and Choi, S. (2015) Oxidation of 5’-dGMP, 5’-dGDP, and 5’-dGTP by a Platinum(IV) Complex. Journal of Biological Inorganic Chemistry, 20, 1327-1341. https://doi.org/10.1007/s00775-015-1312-0
[40]
Bednarski, P.J., Mackay, F.S. and Sadler, P.J. (2007) Photoactivatable Platinum Complexes. Anti-Cancer Agents in Medicinal Chemistry, 7, 75-93. https://doi.org/10.2174/187152007779314053
[41]
Farrell, N.P. (2004) Preclinical Perspectives on the Use of Platinum Compounds in Cancer Chemotherapy. Seminars in Oncology, 31, 1-9. https://doi.org/10.1053/j.seminoncol.2004.11.004
[42]
Dolman, R.C., Deacon, G.B. and Hambley, T.W. (2002) Studies of the Binding of a Series of Platinum(IV) Complexes to Plasma Proteins. Journal of Inorganic Biochemistry, 88, 260-267. https://doi.org/10.1016/S0162-0134(01)00360-9
[43]
Hall, M.D., Alderden, R.A., Zhang, M., et al. (2006) The Fate of Platinum(II) and Platinum(IV) Anti-Cancer Agents in Cancer Cells and Tumours. Journal of Structural Biology, 155, 38-44. https://doi.org/10.1016/j.jsb.2006.01.011
[44]
Choy, H., Park, C. and Yao, M. (2008) Current Status and Future Prospects for Satraplatin, an Oral Platinum Analogue. Clinical Cancer Research, 14, 1633-1638. https://doi.org/10.1158/1078-0432.CCR-07-2176
[45]
Moghaddas, S., Majmudar, P., Marin, R., Dezvareh, H., Qi, C., Soans, E. and Bose, R.N. (2012) Phosphaplatins, Next Generation Platinum Antitumor Agents: A Paradigm Shift in Designing and Defining Molecular Targets. Inorganica Chimica Acta, 393, 173-181. https://doi.org/10.1016/j.ica.2012.05.040
[46]
Varbanov, H., Valiahdi, S.M., Jakupec, M.A., Galanski, M. and Keppler, B.K. (2012) Novel Tetracarboxylatoplatinum(IV) Complexes as Carboplatin Prodrugs. Dalton Transactions, 41, 14404-14415. https://doi.org/10.1039/c2dt31366a
[47]
Reithofer, M., Galanski, M., Roller, A. and Keppler, B.K. (2006) An Entry to Novel Platinum Complexes: Carboxylation of Dihydroxoplatinum(IV) Complexes with Succinic Anhydride and Subsequent Derivatization. European Journal of Inorganic Chemistry, No. 13, 2612-2617. https://doi.org/10.1002/ejic.200600108
[48]
Reithofer, M.R., Valiahdi, S.M., Jakupec, M.A., Arion, V.B., Egger, A., Galanski, M. and Keppler, B.K. (2007) Novel Di- and Tetracarboxylatoplatinum(IV) Complexes. Synthesis, Characterization, Cytotoxic Activity, and DNA Platination. Journal of Medicinal Chemistry, 50, 6692-6699. https://doi.org/10.1021/jm070897b
[49]
Reithofer, M.R., Schwarzinger, A., Valiahdi, S.M., Galanski, M., Jakupec, M.A. and Keppler, B.K. (2008) Novel Bis(carboxylato)dichlorido(ethane-1,2-diamine)platinum(IV) Complexes with Exceptionally High Cytotoxicity. Journal of Inorganic Biochemistry, 102, 2072-2077. https://doi.org/10.1016/j.jinorgbio.2008.07.006
[50]
Varbanov, H., Valiahdi, S.M., Legin, A.A., Jakupec, M.A., Roller, A., Galanski, M. and Keppler, B.K. (2011) Synthesis and Characterization of Novel Bis(carboxylato)dichloridobis(ethylamine)platinum(IV) Complexes with Higher Cytotoxicity than Cisplatin. European Journal of Medicinal Chemistry, 46, 5456-5464. https://doi.org/10.1016/j.ejmech.2011.09.006
[51]
Braddock, P.D., Connors, T.A., Jones, M., Khokhar, A.R., Melzack, D.H. and Tobe, M.L. (1975) Structure and Activity Relationships of Platinum Complexes with Anti-Tumour Activity. Chemico-Biological Interactions, 11, 145-161. https://doi.org/10.1016/0009-2797(75)90095-2
[52]
Hamberger, J., Liebeke, M., Kaiser, M., Bracht, K., Olszewski, U., Zeillinger, R., et al. (2009) Characterization of Chemosensitivity and Resistance of Human Cancer Cell Lines to Platinum(II) versus Platinum(IV) Anticancer Agents. Anti-Cancer Drugs, 20, 559-572. https://doi.org/10.1097/CAD.0b013e32832d513b
[53]
Hamilton, G. (2014) Comparison of Intracellular Stress Response of NCI-H526 Small Cell Lung Cancer (SCLC) Cells to Platinum(II) Cisplatin and Platinum(IV) Oxoplatin. Cancers, 6, 1487-1499. https://doi.org/10.3390/cancers6031487
[54]
Rose, W.C., Crosswell, A.R., Schruig, J.E. and Casazza, A.M. (1993) Preclinical Antitumor Activity of Orally Administered Platinum (IV) Complexes. Cancer Chemotherapy and Pharmacology, 32, 197-203. https://doi.org/10.1007/BF00685835
[55]
McKeage, M.J., Raynaud, F.,Ward, J., Berry, C., O’Dell, D., Kelland, L.R., Murrer, B., Santabarabara, P., Harrap, K.R. and Judson, I.R. (1997) Phase I and Pharmacokinetic Study of an Oral Platinum Complex Given Daily for 5 Days in Patients with Cancer. Journal of Clinical Oncology, 15, 2691-2700. https://doi.org/10.1200/JCO.1997.15.7.2691
[56]
Doshi, G., Sonpavde, G. and Sternberg, C.N. (2012) Clinical and Pharmacokinetic Evaluation of Satraplatin. Expert Opinion on Drug Metabolism & Toxicology, 8, 103-111. https://doi.org/10.1517/17425255.2012.636352
[57]
Hamilton, G. and Olszewski, U. (2013) Picoplatin Pharmacokinetics and Chemotherapy of Non-Small Cell Lung Cancer. Expert Opinion on Drug Metabolism & Toxicology, 9, 1381-1390. https://doi.org/10.1517/17425255.2013.815724
[58]
Figg, W.D., Chau, C.H., Madan, R.A., Gulley, J.L., Gao, R., Sissung, T.M., Spencer, S., Beatson, M., Aragon-Ching, J., Steinberg, S.M. and Dahut, W.L. (2013) Phase II Study of Satraplatin and Prednisone in Patients with Metastatic Castration-Resistant Prostate Cancer: A Pharmacogenetic Assessment of Outcome and Toxicity. Clinical Genitourinary Cancer, 11, 229-237.
[59]
Zák, F., Turánek, J., Kroutil, A., et al. (2004) Platinum(IV) Complex with Adamantylamine as Nonleaving Amine Group: Synthesis, Characterization, and in Vitro Antitumor Activity against a Panel of Cisplatin-Resistant Cancer Cell Lines. Journal of Medicinal Chemistry, 47, 761-763. https://doi.org/10.1021/jm030858+
[60]
Sova, P., Mistr, A., Kroutil, A., Zak, F., Pouckova, P. and Zadinova, M. (2005) Preclinical Anti-Tumor Activity of a New Oral Platinum(IV) Drug LA-12. Anti-Cancer Drugs, 16, 653-657. https://doi.org/10.1097/00001813-200507000-00010
[61]
Shaili, E. (2014) Platinum Anticancer Drugs and Photochemotherapeutic Agents: Recent Advances and Future Developments. Science Progress, 97, 20-40. https://doi.org/10.3184/003685014X13904811808460
[62]
Bown, S.G. (2013) Photodynamic Therapy for Photochemists. Philosophical Transactions of the Royal Society A, 371, 371.
[63]
Farrer, N.J., Salassa, L. and Sadler, P.J. (2009) Photoactivated Chemotherapy (PACT): The Potential of Excited-State d-Block Metals in Medicine. Dalton Transactions, No. 48, 10690-10701. https://doi.org/10.1039/b917753a
[64]
Kratochwil, N.A. and Bednarski, P.J. (1999) Relationships between Reduction Properties and Cancer Cell Growth Inhibitory Activities of cis-Dichloro- and cis-Diiodo-Pt(IV)-ethylenediamines. Archiv der Pharmazie, 332, 279-285. https://doi.org/10.1002/(SICI)1521-4184(19998)332:8<279::AID-ARDP279>3.0.CO;2-1
[65]
Kratochwil, N.A., Zabel, M. and Bednarski, P.J. (1996) Synthesis and X-Ray Crystal Structure of trans,cis-[Pt(OAc)2I2(en)]: A Novel Type of Cisplatin Analog That Can Be Photolyzed by Visible Light to DNA-Binding and Cytotoxic Species in Vitro. Journal of Medicinal Chemistry, 39, 2499-2507. https://doi.org/10.1021/jm9509105
[66]
Kratochwil, N.A., Guo, Z., del Socorro Murdoch, P., Parkinson, J.A., Bednarski, P.J. and Sadler, P.J. (1998) Electron-Transfer-Driven Trans-Ligand Labilization: A Novel Activation Mechanism for Pt(IV) Anticancer Complexes. Journal of the American Chemical Society, 120, 8253-8254. https://doi.org/10.1021/ja980393q
[67]
Westendorf, A.F., Bodtke, A. and Bednarski, P.J. (2011) Studies on the Photoactivation of Two Cytotoxic trans,trans,trans-Diazidodiaminodihydroxo-Pt(IV) Complexes. Dalton Transactions, 40, 5342-5451. https://doi.org/10.1039/c0dt01485k
[68]
Mackay, F.S., Woods, J.A., Moseley, H., Ferguson, J., Dawson, A., Parsons, S. and Sadler, P.J. (2006) A Photoactivated trans-Diammine Platinum Complex as Cytotoxic as Cisplatin. Chemistry: A European Journal, 12, 3155-3161. https://doi.org/10.1002/chem.200501601
[69]
Mackay, F.S., Woods, J.A., Heringová, P., Kaspárková, J., Pizarro, A.M., Moggach, S.A., et al. (2007) A Potent Cytotoxic Photoactivated Platinum Complex. Proceedings of the National Academy of Sciences of the United States of America, 104, 20743-20748. https://doi.org/10.1073/pnas.0707742105
[70]
Westendorf, A.F., Woods, J.A., Korpis, K., Farrer, N.J., Salassa, L., Robinson, K., et al. (2012) Trans,trans,trans-[PtIV(N3)2(OH)2(py)(NH3)]: A Light-Activated Antitumor Platinum Complex That Kills Human Cancer Cells by an Apoptosis-Independent Mechanism. Molecular Cancer Therapeutics, 11, 1894-1904. https://doi.org/10.1158/1535-7163.MCT-11-0959
[71]
Bednarski, P.J., Korpis, K., Westendorf, A.F., Perfahl, S. and Grünert, R. (2013) Effects of Light-Activated Diazido-PtIV Complexes on Cancer Cells in Vitro. Philosophical Transactions of the Royal Society A, 371, Article ID: 20120118. https://doi.org/10.1098/rsta.2012.0118
