Citation: Yan SU, Meng-Meng WANG, Hong-Ke LIU, Zhi SU. Synthesis and Antitumor Properties of Temozolomide-Based Platinum(Ⅳ) Complexes[J]. Chinese Journal of Inorganic Chemistry, ;2022, 38(3): 430-440. doi: 10.11862/CJIC.2022.044 shu

Synthesis and Antitumor Properties of Temozolomide-Based Platinum(Ⅳ) Complexes

Figures(9)

  • Temozolomide is the first-line anticancer drug for the clinical treatment of glioblastoma. In this work, temozolomide was chemically modified and introduced into the platinum(Ⅳ) complex. Two new Pt(Ⅳ) complexes P1T and P2T were successfully synthesized and characterized by 1H NMR and 13C NMR. The results show that both complexes had good lipid solubility with a fast hydrolysis rate. The anticancer activity and the mechanism of P1T and P2T were investigated with the MTT assay, flow cytometry, confocal imaging, and western blot. The results demonstrate that complexes P1T and P2T owned high cytotoxicity to glioma cell line A261, but low toxicity to normal nerve cell HT-22, indicating good cancer cell selectivity. Flow cytometry reveals that complexes P1T and P2T arrest the cell cycle in the G2/M phase, leading to DNA damage and ultimately inducing tumor cell apoptosis.
  • 加载中
    1. [1]

      Louis D N, Perry A, Reifenberger G, Deimling A, Figarella-Branger D, Cavenee W K, Ohgaki H, Wiestler O D, Kleihues P, Ellison D W. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: A Summary[J]. Acta Neuropathol., 2016,131(6):803-820. doi: 10.1007/s00401-016-1545-1

    2. [2]

      Giese A, Bjerkvig R, Berens M E, Westphal M. Cost of Migration: Invasion of Malignant Gliomas and Implications for Treatment[J]. J. Clin. Oncol., 2003,21(8):1624-1636. doi: 10.1200/JCO.2003.05.063

    3. [3]

      Affronti M L, Heery C R, Herndon J E, Rich J N, Reardon D A, Desjardins A, Vredenburgh J J, Friedman A H, Bigner D D, Friedman H S. Overall Survival of Newly Diagnosed Glioblastoma Patients Receiving Carmustine Wafers Followed by Radiation and Concurrent Temozolomide plus Rotational Multiagent Chemotherapy[J]. Cancer, 2009,115(15):3501-3511. doi: 10.1002/cncr.24398

    4. [4]

      de Souza R M, Shaweis H, Han C, Sivasubramaniam V, Brazil L, Beaney R, Sadler G, Al-Sarraj S, Hampton T, Logan J, Hurwitz V, Bhangoo R, Gullan R, Ashkan K. Erratum: Has the Survival of Patients with Glioblastoma Changed over the Years?[J]. Br. J. Cancer, 2016,114(2):146-150. doi: 10.1038/bjc.2015.421

    5. [5]

      Stupp R, Taillibert S, Kanner A, Read W, Steinberg D M, Lhermitte B, Toms S, Idbaih A, Ahluwalia M S, Fink K, Di Meco F, Lieberman F, Zhu J J, Stragliotto G, Tran D D, Brem S, Hottinger A F, Kirson E D, Lavy-Shahaf G, Weinberg U, Kim C Y, Paek S H, Nicholas G, Bruna J, Hirte H, Weller M, Palti Y, Hegi M E, Ram Z. Effect of Tumor-Treating Fields plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial[J]. JAMA - J. Am. Med. Assoc., 2017,318(23):2306-2316. doi: 10.1001/jama.2017.18718

    6. [6]

      Furnari F B, Fenton T, Bachoo R M, Mukasa A, Stommel J M, Stegh A, Hahn W C, Ligon K L, Louis D N, Brennan C, Chin L, DePinho R A, Cavenee W K. Malignant Astrocytic Glioma: Genetics, Biology, and Paths to Treatment[J]. Genes Dev., 2007,21(21):2683-2710. doi: 10.1101/gad.1596707

    7. [7]

      Fan C H, Liu W L, Cao H, Wen C, Chen L, Jiang G. O6-Methylgua-nine DNA Methyltransferase as a Promising Target for the Treatment of Temozolomide-Resistant Gliomas[J]. Cell Death Dis., 2013,4(10)e876. doi: 10.1038/cddis.2013.388

    8. [8]

      Hirose Y, Berger M S, Pieper R O. p53 Effects both the Duration of G2 & M Arrest and the Fate of Temozolomide-Treated Human Glioblas- toma Cells[J]. Cancer Res., 2001,61(5):1957-1963.

    9. [9]

      Friedman H S, Kerby T, Calvert H. Temozolomide and Treatment of Malignant Glioma[J]. Clin. Cancer Res., 2000,6(7):2585-2597.

    10. [10]

      Gerson S L. MGMT: Its Role in Cancer Aetiology and Cancer Thera-peutics[J]. Nat. Rev. Cancer, 2004,4(4):296-307. doi: 10.1038/nrc1319

    11. [11]

      Lee S Y. Temozolomide Resistance in Glioblastoma Multiforme[J]. Genes Dis., 2016,3(3):198-210. doi: 10.1016/j.gendis.2016.04.007

    12. [12]

      Stupp R, Mason W P, van den Bent M J, Weller M, Fisher B, Taphoorn M J B, Belanger K, Brandes A A, Marosi C, Bogdahn U, Curschmann J, Janzer R C, Ludwin S K, Gorlia T, Allgeier A, Lacombe D, Cairncross J G, Eisenhauer E, Mirimanoff R O. Radio-therapy plus Concomitant and Adjuvant Temozolomide for Glioblas-toma[J]. N. Engl. J. Med., 2005,352(10):987-996. doi: 10.1056/NEJMoa043330

    13. [13]

      Stupp R, Hegi M E, Mason W P, Bent M J, Taphoorn M J B, Janzer R C, Ludwin S K, Allgeier A, Fisher B, Belanger K, Hau P, Brandes A A, Gijtenbeek J, Marosi C, Vecht C J, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross J G, Mirimanoff R O. Effects of Radiotherapy with Concomitant and Adjuvant Temozolomide versus Radiotherapy Alone on Survival in Glioblastoma in a Randomised Phase Ⅲ Study: 5-Year Analysis of the EORTC-NCIC Trial[J]. Lancet Oncol., 2009,10(5):459-466. doi: 10.1016/S1470-2045(09)70025-7

    14. [14]

      Rosenberg B, Vancamp L, Trosko J E, Mansour V H. Platinum Com- pounds: A New Class of Potent Antitumour Agents[J]. Nature, 1969,222(5191):385-386. doi: 10.1038/222385a0

    15. [15]

      Wang X H, Wang X Y, Jin S X, Muhammad N, Guo Z J. Stimuli-Responsive Therapeutic Metallodrugs[J]. Chem. Rev., 2019,119(2):1138-1192. doi: 10.1021/acs.chemrev.8b00209

    16. [16]

      JIN S X, GUO Z J, WANG X Y. Antitumor Metal Complexes Target-ing Energy Metabolism[J]. Progress in Pharmaceutical Sciences, 2020,44(4):280-293.

    17. [17]

      Klein A V, Hambley T W. Platinum Drug Distribution in Cancer Cells and Tumors[J]. Chem. Rev., 2009,109(10):4911-4920. doi: 10.1021/cr9001066

    18. [18]

      Dilruba S, Kalayda G V. Platinum-Based Drugs: Past, Present and Future[J]. Cancer Chemother. Pharmacol., 2016,77(6):1103-1124. doi: 10.1007/s00280-016-2976-z

    19. [19]

      Galluzzi L, Senovilla L, Vitale I, Michels J, Martins I, Kepp O, Castedo M, Kroemer G. Molecular Mechanisms of Cisplatin Resis-tance[J]. Oncogene, 2012,31(15):1869-1883. doi: 10.1038/onc.2011.384

    20. [20]

      Galluzzi L, Vitale I, Michels J, Brenner C, Szabadkai G, Harel-Bel-lan A, Castedo M, Kroemer G. Systems Biology of Cisplatin Resis-tance: Past, Present and Future[J]. Cell Death Dis., 2014,5(5)e1257. doi: 10.1038/cddis.2013.428

    21. [21]

      Wang X Y, Guo Z J. Targeting and Delivery of Platinum-Based Anti-cancer Drugs[J]. Chem. Soc. Rev., 2013,42(1):202-224. doi: 10.1039/C2CS35259A

    22. [22]

      Oun R, Moussa Y E, Wheate N J. The Side Effects of Platinum-Based Chemotherapy Drugs: A Review for Chemists[J]. Dalton Trans., 2018,47(19):6645-6653. doi: 10.1039/C8DT00838H

    23. [23]

      Karasawa T, Steyger P S. An Integrated View of Cisplatin-Induced Nephrotoxicity and Ototoxicity[J]. Toxicol. Lett., 2015,237(3):219-227. doi: 10.1016/j.toxlet.2015.06.012

    24. [24]

      Johnstone T C, Suntharalingam K, Lippard S J. The Next Generation of Platinum Drugs: Targeted Pt Agents, Nanoparticle Delivery, and Pt Prodrugs[J]. Chem. Rev., 2016,116(5):3436-3486. doi: 10.1021/acs.chemrev.5b00597

    25. [25]

      Wilson J J, Lippard S J. Synthetic Methods for the Preparation of Platinum Anticancer Complexes[J]. Chem. Rev., 2014,114(8):4470-4495. doi: 10.1021/cr4004314

    26. [26]

      Hall M D, Hambley T W. Platinum Antitumour Compounds: Their Bioinorganic Chemistry[J]. Coord. Chem. Rev., 2002,232(1):49-67.

    27. [27]

      Jin S X, Hao Y Y, Zhu Z Z, Muhammad N, Zhang Z Q, Wang K, Guo Y, Guo Z J, Wang X Y. Impact of Mitochondrion-Targeting Group on the Reactivity and Cytostatic Pathway of Platinum Complexes[J]. Inorg. Chem., 2018,57(17):11135-11145. doi: 10.1021/acs.inorgchem.8b01707

    28. [28]

      Shi Y, Liu S A, Kerwood D J, Goodisman J, Dabrowiak J C. Pt Complexes as Prodrugs for Cisplatin[J]. J. Inorg. Biochem., 2012,107(1):6-14. doi: 10.1016/j.jinorgbio.2011.10.012

    29. [29]

      Arrowsmith J, Jennings S A, Clark A S, Stevens M F G. Antitumor Imidazotetrazines. 41. Conjugation of the Antitumor Agents Mitozolo-mide and Temozolomide to Peptides and Lexitropsins Bearing DNA Major and Minor Groove-Binding Structural Motifs[J]. J. Med. Chem., 2002,45(25):5458-5470.

    30. [30]

      Huang H Y, Yu B L, Zhang P Y, Huang J J, Chen Y, Gasser G, Ji L N, Chao H. Highly Charged Ruthenium Polypyridyl Complexes as Lysosome-Localized Photosensitizers for Two-Photon Photodynamic Therapy[J]. Angew. Chem. Int. Ed., 2015,54(47):14049-14052. doi: 10.1002/anie.201507800

    31. [31]

      Huang H Y, Zhang P Y, Yu B L, Chen Y, Wang J Q, Ji L N, Chao H. Targeting Nucleus DNA with a Cyclometalated Dipyridophenazineru-thenium Complex[J]. J. Med. Chem., 2014,57(21):8971-8983. doi: 10.1021/jm501095r

    32. [32]

      Oldfield S P, Hall M D, Platts J A. Calculation of Lipophilicity of a Large, Diverse Dataset of Anticancer Platinum Complexes and the Relation to Cellular Uptake[J]. J. Med. Chem., 2007,50(21):5227-5237. doi: 10.1021/jm0708275

    33. [33]

      Bonner W M, Redon C E, Dickey J S, Nakamura A J, Sedelnikova O A, Solier S, Pommier Y. γH2AX and Cancer[J]. Nat. Rev. Cancer, 2008,8(12):957-967. doi: 10.1038/nrc2523

    34. [34]

      Revet I, Feeney L, Bruguera S, Wilson W, Dong T K, Oh D H, Dankort D, Cleaver J E. Functional Relevance of the Histone γH2Ax in the Response to DNA Damaging Agents[J]. Proc. Natl. Acad. Sci. U. S. A., 2011,108(21):8663-8667. doi: 10.1073/pnas.1105866108

    35. [35]

      Shieh S Y, Ikeda M, Taya Y, Prives C. DNA Damage-Induced Phos-phorylation of p53 Alleviates Inhibition by MDM2[J]. Cell, 1997,91(3):325-334. doi: 10.1016/S0092-8674(00)80416-X

    36. [36]

      Wang D, Lippard S J. Cellular Processing of Platinum Anticancer Drugs[J]. Nat. Rev. Drug Discovery, 2005,4(4):307-320. doi: 10.1038/nrd1691

    37. [37]

      Zhou Z J, Song J B, Nie L M, Chen X Y. Reactive Oxygen Species Generating Systems Meeting Challenges of Photodynamic Cancer Therapy[J]. Chem. Soc. Rev., 2016,45(23):6597-6626. doi: 10.1039/C6CS00271D

    38. [38]

      WU J, TAO Q, GE C, XUE X L, QIAN Y, LIU H K. Synthesis and Antitumor Properties of Ruthenium-Arene Complexes Based on Nat-ural Product Perillol[J]. Chinese J. Inorg. Chem., 2020,36(7):1223-1232.  

    39. [39]

      Wang F X, Liang J H, Zhang H, Wang Z H, Wan Q, Tan C P, Ji L N, Mao Z W. Mitochondria-Accumulating Rhenium Tricarbonyl Com-plexes Induce Cell Death via Irreversible Oxidative Stress and Gluta-thione Metabolism Disturbance[J]. ACS Appl. Mater. Interfaces, 2019,11(14):13123-13133. doi: 10.1021/acsami.9b01057

    40. [40]

      Carneiro B A, El-Deiry W S. Targeting Apoptosis in Cancer Therapy[J]. Nat. Rev. Clin. Oncol., 2020,17(7):395-417. doi: 10.1038/s41571-020-0341-y

  • 加载中
    1. [1]

      Chunmei GUOWeihan YINJingyi SHIJianhang ZHAOYing CHENQuli FAN . Facile construction and peroxidase-like activity of single-atom platinum nanozyme. Chinese Journal of Inorganic Chemistry, 2024, 40(9): 1633-1639. doi: 10.11862/CJIC.20240162

    2. [2]

      Qilu DULi ZHAOPeng NIEBo XU . Synthesis and characterization of osmium-germyl complexes stabilized by triphenyl ligands. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1088-1094. doi: 10.11862/CJIC.20240006

    3. [3]

      Haitang WANGYanni LINGXiaqing MAYuxin CHENRui ZHANGKeyi WANGYing ZHANGWenmin WANG . Construction, crystal structures, and biological activities of two Ln3 complexes. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1474-1482. doi: 10.11862/CJIC.20240188

    4. [4]

      Jingjing QINGFan HEZhihui LIUShuaipeng HOUYa LIUYifan JIANGMengting TANLifang HEFuxing ZHANGXiaoming ZHU . Synthesis, structure, and anticancer activity of two complexes of dimethylglyoxime organotin. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1301-1308. doi: 10.11862/CJIC.20240003

    5. [5]

      Xin MAYa SUNNa SUNQian KANGJiajia ZHANGRuitao ZHUXiaoli GAO . A Tb2 complex based on polydentate Schiff base: Crystal structure, fluorescence properties, and biological activity. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1347-1356. doi: 10.11862/CJIC.20230357

    6. [6]

      Yingchun ZHANGYiwei SHIRuijie YANGXin WANGZhiguo SONGMin WANG . Dual ligands manganese complexes based on benzene sulfonic acid and 2, 2′-bipyridine: Structure and catalytic properties and mechanism in Mannich reaction. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1501-1510. doi: 10.11862/CJIC.20240078

    7. [7]

      Zhaoyang WANGChun YANGYaoyao SongNa HANXiaomeng LIUQinglun WANG . Lanthanide(Ⅲ) complexes derived from 4′-(2-pyridyl)-2, 2′∶6′, 2″-terpyridine: Crystal structures, fluorescent and magnetic properties. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1442-1451. doi: 10.11862/CJIC.20240114

    8. [8]

      Xinting XIONGZhiqiang XIONGPanlei XIAOXuliang NIEXiuying SONGXiuguang YI . Synthesis, crystal structures, Hirshfeld surface analysis, and antifungal activity of two complexes Na(Ⅰ)/Cd(Ⅱ) assembled by 5-bromo-2-hydroxybenzoic acid ligands. Chinese Journal of Inorganic Chemistry, 2024, 40(9): 1661-1670. doi: 10.11862/CJIC.20240145

    9. [9]

      Yuanpei ZHANGJiahong WANGJinming HUANGZhi HU . Preparation of magnetic mesoporous carbon loaded nano zero-valent iron for removal of Cr(Ⅲ) organic complexes from high-salt wastewater. Chinese Journal of Inorganic Chemistry, 2024, 40(9): 1731-1742. doi: 10.11862/CJIC.20240077

    10. [10]

      Yujia LITianyu WANGFuxue WANGChongchen WANG . Direct Z-scheme MIL-100(Fe)/BiOBr heterojunctions: Construction and photo-Fenton degradation for sulfamethoxazole. Chinese Journal of Inorganic Chemistry, 2024, 40(3): 481-495. doi: 10.11862/CJIC.20230314

    11. [11]

      Zongfei YANGXiaosen ZHAOJing LIWenchang ZHUANG . Research advances in heteropolyoxoniobates. Chinese Journal of Inorganic Chemistry, 2024, 40(3): 465-480. doi: 10.11862/CJIC.20230306

    12. [12]

      Chuanming GUOKaiyang ZHANGYun WURui YAOQiang ZHAOJinping LIGuang LIU . Performance of MnO2-0.39IrOx composite oxides for water oxidation reaction in acidic media. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1135-1142. doi: 10.11862/CJIC.20230459

    13. [13]

      Endong YANGHaoze TIANKe ZHANGYongbing LOU . Efficient oxygen evolution reaction of CuCo2O4/NiFe-layered bimetallic hydroxide core-shell nanoflower sphere arrays. Chinese Journal of Inorganic Chemistry, 2024, 40(5): 930-940. doi: 10.11862/CJIC.20230369

    14. [14]

      Qiangqiang SUNPengcheng ZHAORuoyu WUBaoyue CAO . Multistage microporous bifunctional catalyst constructed by P-doped nickel-based sulfide ultra-thin nanosheets for energy-efficient hydrogen production from water electrolysis. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1151-1161. doi: 10.11862/CJIC.20230454

    15. [15]

      Yan LIUJiaxin GUOSong YANGShixian XUYanyan YANGZhongliang YUXiaogang HAO . Exclusionary recovery of phosphate anions with low concentration from wastewater using a CoNi-layered double hydroxide/graphene electronically controlled separation film. Chinese Journal of Inorganic Chemistry, 2024, 40(9): 1775-1783. doi: 10.11862/CJIC.20240043

Metrics
  • PDF Downloads(0)
  • Abstract views(748)
  • HTML views(143)

通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索
Address:Zhongguancun North First Street 2,100190 Beijing, PR China Tel: +86-010-82449177-888
Powered By info@rhhz.net

/

DownLoad:  Full-Size Img  PowerPoint
Return