基于糖基化修饰的铂类抗肿瘤化合物研究进展

张强, 李绍青, 刘薇, 邵佳, 田金磊, 魏金霞

中国药学杂志 ›› 2020, Vol. 55 ›› Issue (17) : 1409-1414.

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中国药学杂志 ›› 2020, Vol. 55 ›› Issue (17) : 1409-1414. DOI: 10.11669/cpj.2020.17.002
综述

基于糖基化修饰的铂类抗肿瘤化合物研究进展

  • 张强1, 李绍青1, 刘薇1, 邵佳2*, 田金磊1*, 魏金霞3
作者信息 +

Progress in Study of Platinum Antitumor Compounds Modified by Glycosylation

  • ZHANG Qiang1, LI Shao-qing1, LIU Wei1, SHAO Jia2*, TIAN Jin-lei1*, WEI Jin-xia3
Author information +
文章历史 +

摘要

铂类药物是众多恶性肿瘤的关键治疗药物之一,然而传统铂类药物对肿瘤细胞靶向性差,存在明显的毒副作用,因而亟须提升铂类药物靶向性来增加其抗肿瘤活性。糖及其衍生物是机体细胞间传递信息不可或缺的基础物质,肿瘤细胞通过Warburg效应可对含有特定糖分子结构的药物分子产生特异性识别并有效吸收,通过对传统铂类药物进行糖基功能化修饰可有效提升其对肿瘤细胞的选择性。此外,通过合理的糖基化修饰,还可明显提升铂类药物的靶向性和水溶性,并有效降低其毒性,因此,对铂类化合物进行糖基化修饰是铂类药物研究领域的热点之一。基于此,笔者综述了近年来糖基化铂类化合物在抗肿瘤领域的研究进展。

Abstract

Platinum drugs are one of the key therapeutic drugs for many malignant tumors, but traditional platinum drugs have poor tumor targeting effect and obvious side effects, so it is necessary to improve the targeting of platinum drugs for increasing their antitumor activity. Sugars and their derivatives are indispensable substances for the transmission of information between cells. Tumor cells can specifically recognize, and effectively absorb drug molecules containing specific sugar through Warburg effect. The selectivity of traditional platinum drugs to tumor cells can be effectively improved by functional glycosylation. In addition, with reasonable glycosylation, there is significant improvement in the targeting effect and water solubility of platinum drugs, with low collateral effects. Therefore, the design of glycosyl platinum compounds is one of the hotspots in the field of anticancer platinum drugs. Based on the above background, the research progress in glycosylated platinum compounds in the field of antitumor treatment is reviewed.

关键词

糖基化 / 铂类化合物 / 抗肿瘤活性

Key words

glycosylation / platinum compound / antitumor activity

引用本文

导出引用
张强, 李绍青, 刘薇, 邵佳, 田金磊, 魏金霞. 基于糖基化修饰的铂类抗肿瘤化合物研究进展[J]. 中国药学杂志, 2020, 55(17): 1409-1414 https://doi.org/10.11669/cpj.2020.17.002
ZHANG Qiang, LI Shao-qing, LIU Wei, SHAO Jia, TIAN Jin-lei, WEI Jin-xia. Progress in Study of Platinum Antitumor Compounds Modified by Glycosylation[J]. Chinese Pharmaceutical Journal, 2020, 55(17): 1409-1414 https://doi.org/10.11669/cpj.2020.17.002
中图分类号: R914.5   

参考文献

[1] JOHNSTONE T C, SUNTHARALINGAM K, LIPPARD S J. The next generation of platinum drugs: targeted Pt(Ⅱ) agents, nanoparticle delivery, and Pt(Ⅳ) prodrugs [J]. Chem Rev, 2016, 116(5):3436-3486.
[2] WANG X Y, GUO Z J. Targeting and delivery of platinum-based anticancer drugs [J]. Chem Soc Rev, 2013, 42(1):202-224.
[3] COUNIHAN J L, GROSSMAN E A, NOMURA D K. Cancer metabolism: current understanding and therapies [J]. Chem Rev, 2018, 118(14):6893-6923.
[4] KENNY R G, MARMION C J. Toward multi-targeted platinum and ruthenium drugs-a new paradigm in cancer drug treatment regimens? [J]. Chem Rev, 2019, 119(2):1058-1137.
[5] KENNY R G, CHUAH S W, CRAWFORD A, et al. Platinum(Ⅳ) prodrugs-a step closer to Ehrlich′s vision? [J]. Eur J Inorg Chem, 2017, 2017(12): 1596-1612.
[6] MA D L, SHUM T Y, ZHANG F, et al. Water soluble luminescent platinum terpyridine complexes with glycosylated acetylide and arylacetylide ligands: photoluminescent properties and cytotoxicities [J]. Chem Commun (Camb), 2005, 37:4675-4677.
[7] RAMU V, GAUTAM S, GARAI A, et al. Glucose-appended platinum(Ⅱ)-BODIPY conjugates for targeted photodynamic therapy in red light [J]. Inorg Chem, 2018, 57(4):1717-1726.
[8] BERGER I, NAZAROV A A, HARTINGER C G, et al. A glucose derivative as natural alternative to the cyclohexane-1,2-diamine ligand in the anticancer drug oxaliplatin? [J]. Chem Med Chem, 2007, 2(4):505-514.
[9] MIKATA Y, SHINOHARA Y, YONEDA K, et al. Unprecedented sugar-dependent in vivo antitumor activity of carbohydrate-pendant cis-diamminedichloroplatinum(Ⅱ) complexes[J]. Bioorg Med Chem Lett, 2001, 11(23):3045-3047.
[10] YANO S, OHIC H, ASHIZAKID M, et al. Syntheses, characterization, and antitumor activities of platinum(Ⅱ) and palladium(Ⅱ) complexes with sugar-conjugated triazole ligands[J]. Chem Biodivers, 2012, 9(9):1903-1915.
[11] CHEN Y, HEEG M J, BRAUNSCHWEIGER P, et al. A carbohydrate-linked cisplatin analogue having antitumor activity[J]. Angew Chem, 1999, 111(12):1882-1884.
[12] SHI J C, TONG Q S, JIA L. et al. Carbohydrate derivative, platinum complex with anticancer effect and preparation method thereof: China, 200610172630.2[P]. 20070711.
[13] MÖKER J, THIEM J. Synthesis of novel gluco- and galacto-functionalized platinum complexes[J]. Eur J Org Chem, 2009, 2009(28):4842-4847.
[14] CUCCIOLITO M E, LITTO R D, FANIZZI F P, et al. Hydrophilic ligands derived from glucose: synthesis, characterization and in vitro cytotoxic activity on cancer cells of Pt(Ⅱ) complexes[J]. Inorg Chim Acta, 2010, 363(4):741-747.
[15] CUCCIOLITO M E, DE LUCA BOSSA F, ESPOSITO R, et al. C-Glycosylation in platinum-based agents: a viable strategy to improve cytotoxicity and selectivity[J]. Inorg Chem Front, 2018,5:2921-2933.
[16] CUCCIOLITO M E, D′AMORA A, DE FEO G, et al. Five-coordinate platinum(Ⅱ) compounds containing sugar ligands: synthesis, characterization, cytotoxic activity, and interaction with biological macromolecules[J]. Inorg Chem, 2018, 57(6):3133-3143.
[17] ANNUNZIATA A, CUCCIOLITO M E, ESPOSITO R, et al. A highly efficient and selective antitumor agent based on a glucoconjugated carbene platinum(ii) complex[J]. Dalton Trans, 2019, 48(22):7794-7800.
[18] PATRA M, AWUAH S G, LIPPARD S J. Chemical approach to positional isomers of glucose-platinum conjugates reveals specific cancer targeting through glucose-transporter-mediated uptake in vitro and in vivo[J]. Am Chem Soc,2016,138(38):12541-12551.
[19] PATRA M, JOHNSTONE T C, SUNTHARALINGAM K, et al. A potent glucose-platinum conjugate exploits glucose transporters and preferentially accumulates in cancer cells[J]. Angew Chem, 2016, 55(7):2550-2554.
[20] LIU P, LU Y, GAO X, et al. Highly water-soluble platinum(Ⅱ) complexes as GLUT substrates for targeted therapy: improved anticancer efficacy and transporter-mediated cytotoxic properties[J]. Chem Commun (Camb), 2013, 49(24):2421-2423.
[21] GAO X, LIU S, SHI Y, et al. Mechanistic and biological characteristics of different sugar conjugated 2-methyl malonatoplatinum(Ⅱ) complexes as new tumor targeting agents[J]. Eur J Med Chem, 2017, 125:372-384.
[22] HAN J, GAO X, LIU R, et al. Design, synthesis of novel platinum(Ⅱ) glycoconjugates, and evaluation of their antitumor effects[J]. Chem Biol Drug Des, 2016, 87(6):867-877.
[23] LI H, GAO X, LIU R, et al. Glucose conjugated platinum(Ⅱ) complex: antitumor superiority to oxaliplatin, combination effect and mechanism of action[J]. Eur J Med Chem, 2015, 101: 400-408.
[24] LIU R, FU Z, ZHAO M, et al. GLUT1-mediated selective tumor targeting with fluorine containing platinum(Ⅱ) glycoconjugates[J]. Oncotarget, 2017, 8(24):39476-39496.
[25] LIU R, LI H, GAO X, et al. Mannose-conjugated platinum complexes reveals effective tumor targeting mediated by glucose transporter 1[J]. Biochem Biophys Res Commun, 2017, 487(1):34-40.
[26] MI Q, MA Y, GAO X, et al. 2-Deoxyglucose conjugated platinum (Ⅱ) complexes for targeted therapy: design, synthesis, and antitumor activity[J]. J Biomol Struct Dyn, 2016, 34(11):2339-2350.
[27] WU M, LI H, LIU R, et al. Galactose conjugated platinum(Ⅱ) complex targeting the Warburg effect for treatment of non-small cell lung cancer and colon cancer[J]. Eur J Med Chem, 2016, 110: 32-42.
[28] LI T, GAO X, YANG L, et al. Methyl 6-amino-6-deoxy-d-pyranoside-conjugated platinum(Ⅱ) complexes for glucose transporter (GLUT)-mediated tumor targeting: synthesis, cytotoxicity, and cellular uptake mechanism[J]. Chem Med Chem, 2016,11(10):1069-1077.
[29] GABANO E, RAVERA M, OSELLA D. Pros and cons of bifunctional platinum(Ⅳ) antitumor prodrugs: two are (not always) better than one[J]. Dalton Trans, 2014, 43(26):9813-9820.
[30] WANG Q P, HUANG Z L, MA J, et al. Design, synthesis and biological evaluation of a novel series of glycosylated platinum(Ⅳ) complexes as antitumor agents[J]. Dalton Trans, 2016, 45(25):10366-10374.
[31] MA J, WANG Q, YANG X, et al. Glycosylated platinum(Ⅳ) prodrugs demonstrated significant therapeutic efficacy in cancer cells and minimized side-effects[J]. Dalton Trans, 2016, 45(29):11830-11838.
[32] MA J, YANG X, HAO W, et al. Mono-functionalized glycosylated platinum(Ⅳ) complexes possessed both pH and redox dual-responsive properties: exhibited enhanced safety and preferentially accumulated in cancer cells in vitro and in vivo[J]. Eur J Med Chem, 2017, 128: 45-55.
[33] MA J, WANG Q, HUANG Z, et al. 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]. J Med Chem, 2017, 60(13):5736-5748.
[34] MA J, LIU H, XI Z, et al. Protected and de-protected platinum(Ⅳ) glycoconjugates with GLUT1 and OCT2-mediated selective cancer targeting: demonstrated enhanced transporter-mediated cytotoxic properties in vitro and in vivo[J]. Front Chem, 2018, 6: 386.
[35] WANG H F, YANG X D, ZHAO C L, et al. Glucose-conjugated platinum(Ⅳ) complexes as tumor-targeting agents: design, synthesis and biological evaluation[J]. Bioorg Med Chem, 2019, 27(8):1639-1645.
[36] HOLLIS L S, STERN E W. Cis-Diamineplatinum complexes with diphosphonates as antitumor agents: US, 90307746.9[P]. 1991-04.
[37] SACHINVALA N D, CHEN H.Novel sucrose ligands, methods for their preparation, platinum complexesderived therefrom, and methods for their usage:US, PCT/US93/06166[P]. 1993-07-29.
[38] SACHINVALA N D, CHEN H, NIEMCZURA W P, et al. Synthesis, characterization, and anticancer activities of the first platinum complexes from sucrose[J]. Med Chem, 1993, 36(12):1791-1795.

基金

国家自然科学基金项目资助(81803356,81703690);天津市自然科学基金项目资助(19JCQNJC12200);天津市第一中心医院科技基金资助(院CM201806)
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