|Table of Contents|

Research progress on anti-tumor effect of TNBG and its derivatives

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

2023 13
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Research progress on anti-tumor effect of TNBG and its derivatives
CHEN Jiezhong1ZHENG Xiaohong2YU Yu3
1.Department of Medical Nursing,Jiyuan Vocational and Technical College,Henan Jiyuan 459000,China;2.School of Pharmacy,Chongqing Medical and Pharmaceutical College,Chongqing 401331,China;3.College of Pharmaceutical Science,Chongqing Medicinal University,Chongqing 400016,China.
TNBGtumordruglipid metabolism
Lipid metabolism plays an important role in tumor development and invasion,and has become one of the most important metabolic markers of tumor cells.PPARγ ligands or agonists have good anti-tumor effects on a variety of tumors.TNBG is an innovative anti-tumor drug developed independently.In vitro and in vivo experiments show that it has significant anti-tumor effect,presenting non cytotoxicit.It has been confirmed that PPARγ is its target.In this paper,the anti-tumor effects and mechanisms of TNBG and its derivatives are reviewed.


[1]BROADFIELD LA,PANE AA,TALEBI A,et al.Lipid metabolism in cancer:New perspectives and emerging mechanisms[J].Dev Cell,2021,56(10):1363-1393.
[2]SUN Z,JIANG Q,LI J,et al.The potent roles of Salt-Inducible Kinases (SIKs) in metabolic homeostasis and tumorigenesis[J].Signal Transduct Target Ther,2020,5(1):150.
[3]LLU RZ,GODBOUT R.An amplified fatty acid-binding protein gene cluster in prostate cancer:emerging roles in lipid metabolism and metastasis[J].Cancers,2020,12(12):3823.
[4]HUANG S,GUO Y,LI Z,et al.Systematic review of metabolomic profiling of gastric cancer and esophageal cancer[J].Cancer Biol Med,2020,17(1):181-198.
[5]CHENG S,WANG G,WANG Y,et al.Fatty acid oxidation inhibitor etomoxir suppresses tumor progression and induces cell cycle arrest via PPARγ-mediated pathway in bladder cancer[J].Clin Sci,2019,133(15):1745-1758.
[6]RHRIG F,SCHULZE A.The multifaceted roles of fatty acid synthesis in cancers[J].Nat Rev Cancer,2016,16(11):732-749.
[7]SNAEBJORNSSON MT,JANAKI-RAMAN S,SCHULZE A.Greasing the wheels of the cancer machine:the role of lipid metabolism in cancers[J].Cell Metab,2020,31(1):62-76.
[8]余瑜.一种氮杂甾体化合物制备及其用途[P].中国,CN1124251A,1996-06-12. YU Y.A kind of aza-steroid compound preparation and use[P].China,CN1124251A,1996-06-12.
[9]余瑜,李龙江,汤为学,等.创新构型非细胞毒性抗肿瘤新药TNBG新作用机制的研究[C].上海:中国科协第五届青年学术年会论文集,2004:253-254. YU Y,LI LJ,TANG WX,et al.Study on the new mechanism of non cytotoxic anti-tumor drug TNBG with innovative configuration[C].Shanghai:Proceedings of the Fifth Youth Academic Annual Conference of China Association for Science and Technology,2004:253-254.
[10]刘嫱,陈志琼,杨菲,等.反相高效液相色谱法测定小鼠血浆中德氮吡格[J].西南大学学报(自然科学版),2008,30(07):117-120. LIU Q,CHEN ZQ,YANG F,et al.Determination of TNBG in plasma by RP-HPLC[J].Journal of Southwest University (Natural Science Edition),2008,30(07):117-120.
[11]YUAN Y,LI W,LI L,et al.Effects of tetrazanbigen on the protein expression in human hepatocellular carcinoma cell line QGY-7701[J].J Huazhong Univ Sci Technolog Med Sci,2009,29(3):304-308.
[12]陈洁忠,郑小红,段雯,等.1-氯甲基-1,2,3,4-四氢异喹啉盐酸盐的制备[J].中国医药工业杂志,2009,40(03):178-179. CHEN JZ,ZHENG XH,DUAN W,et al.Preparation of 1-chloromethyl-1,2,3,4-tetrahydroisoquinoline hydrochloride[J].Chinese Journal of Pharmaceuticals,2009,40(03):178-179.
[13]程训官,郑小红,夏铸,等.1-氨甲基-1,2,3,4-四氢异喹啉的合成研究[C].重庆:中国化学会全国第三届有机合成化学与过程学术讨论会论文摘要集,2010:174-175. CHENG XG,ZHENG XH,XIA Z,et al.Synthesis of 1-aminomethyl-1,2,3,4-tetrahydroisoquinoline hydrochloride[C].Chongqing:Abstracts of the Third National Symposium on Organic Synthetic Chemistry and Processes,Chinese Chemical Society,2010:174-175.
[14]罗宗伟.喹喔啉及其衍生物的合成研究[D].重庆:重庆医科大学,2007. LUO ZW.Synthesis of quinoxaline and its derivatives[D].Chongqing:Chongqing Medical University,2007.
[15]甘淋玲.新型抗肿瘤TNBG衍生物的设计合成及构效关系研究[D].重庆:重庆医科大学,2020. GAN LL.Design,synthesis and structure-activity relationship of novel TNBG derivatives as antitumor agent[D].Chongqing:Chongqing Medical University,2020.
[16]LI LJ,YU Y,TANG WX,et al.Effects of TNBG on the proliferation and apoptosis of human hepatocellular carcinoma cell line QGY-7701[J].Journal of Sichuan University(Medical Science Edition),2005,36(3):372-374.
[17]YOON H,SHAW JL,HAIGIS MC,et al.Lipid metabolism in sickness and in health:Emerging regulators of lipotoxicity[J].Mol Cell,2021,81(18):3708-3730.
[18]李龙江.创新构型抗肿瘤新药德氮吡格的作用机制探讨[D].重庆:重庆医科大学,2005. LI LJ.A survey on the mechanism of a new antitumor drug TNBG with novel configuratton[D].Chongqing:Chongqing Medical University,2005.
[19]ELIX C,PAL SK,JONES JO.The role of peroxisome proliferator-activated receptor gamma in prostate cancer[J].Asian J Androl,2018,20(3):238-243.
[20]WILSON HE,STANTON DA,RELLICK S,et al.Breast cancer-associated skeletal muscle mitochondrial dysfunction and lipid accumulation is reversed by PPARG[J].Am J Physiol Cell Physiol,2021,320(4):C577-C590.
[21]BUROTTO M,SZABO E.PPARγ in head and neck cancer prevention[J].Oral Oncol,2014,50(10):924-929.
[22]MATSUDA M,KORN BS,HAMMER RE,et al.SREBP cleavage-activating protein (SCAP) is required for increased lipid synthesis in liver induced by cholesterol deprivation and insulin elevation[J].Genes Dev,2001,15(10):1206-1216.
[23]袁拥华,杨晓兰,李伟,等.德氮吡格对人肝癌细胞QGY-7701的亚细胞蛋白质组学研究[C].重庆:2009年脂质代谢与器官损害国际学术研讨会论文摘要集,2009:149-150. YUAN YH,YANG XL,LI W,et al.Subcellular proteomic analysis of Tetrazanbigen on human hepatocellular carcinoma cell line QGY-7701[C].Chongqing:Abstracts of International Symposium on Lipid Metabolism and Organ Damage in 2009,2009:149-150.
[24]李龙江,杨晓兰,袁拥华,等.德氮吡格对人肝癌细胞株QGY-7701基因表达的影响[J].第三军医大学学报,2006,28(02):151-153. LI LJ,YANG XL,YUAN YH,et al.Changes of gene expression of human hepatocellular carcinoma cell line QGY-7701 induced by tetrazanbigen[J].Acta Academiae Medicinae Militaris Tertiae,2006,28(02):151-153.
[25]FAN X,XU D,LU B,et al.Improving the refolding of NTA protein by urea gradient and arginine gradient size-exclusion chromatography[J].J Biochem Biophys Methods,2008,70(6):1130-1138.
[26]FONSECA RG,FERREIRA TL,WARD RJ.Refolding and purification of the human secreted group IID phospholipase A2 expressed as inclusion bodies in Escherichia coli[J].Protein Expr Purif,2009,67(2):82-87.
[27]李伟,张雪梅,郑晓红,等.尺寸排阻色谱柱上尿素梯度复性全长人PPAR-γ[J].光谱实验室,2010,27(04):1614-1620. LI W,ZHANG XM,ZHENG XH,et al.On-column refolding of full-length human PPAR-γ by urea gradient size-exclusion chromatography[J].Chinese Journal of Spectroscopy Laboratory,2010,27(04):1614-1620.
[28]李伟.创新抗癌药徳氮吡格作用PPARγ靶点的研究[D].重庆:重庆医科大学,2009. LI W.Study on PPARγ target for novel antitumour drug tetraznbigen[D].Chongqing:Chongqing Medical University,2009.
[29]LOS M,BUREK CJ,STROH C,et al.Anticancer drugs of tomorrow:apoptotic pathways as targets for drug design[J].Drug Discov Today,2003,8(2):67-77.
[30]SGAL-BENDIRDJIAN E,HILLION J,BELMOKHTAR CA.Current concepts on apoptotic signalling pathways:new targets for anticancer strategies[J].Bull Cancer,2003,90(1):9-17.
[31]UNGER RH.The physiology of cellular liporegulation[J].Annu Rev Physiol,2003,65:333-347.
[32]STRAUSS B,HARRISON A,COELHO PA,et al.Cyclin B1 is essential for mitosis in mouse embryos,and its nuclear export sets the time for mitosis[J].J Cell Biol,2018,217(1):179-193.
[33]YE C,WANG J,WU P,et al.Prognostic role of cyclin B1 in solid tumors:a meta-analysis[J].Oncotarget,2017,8(2):2224-2232.
[34]李龙江,陈志琼,汤为学,等.德氮吡格对人肝癌细胞株增殖抑制的体外研究[J].重庆医科大学学报,2005,30(03):345-347. LI LJ,CHEN ZQ,TANG WX,et al.Inhibition of proliferation of human hepatocellular carcinoma cell lines by TNBG in vitro[J].Journal of Chongqing Medical University,2005,30(03):345-347.
[35]郑小红,李伟,张昕宇,等.新型手性抗肿瘤药物德氮吡格(TNBG)体外抗肿瘤活性初步研究[J].世界科技研究与发展,2011,33(3):477-480. ZHENG XH,LI W,ZHANG XY,et al.Researches on antitumor activity of novel chiral compound TNBG in vitro[J].World Sci-Tech R & D,2011,33(3):477-480.
[36]郑小红.创新脂毒性抗癌药物德氮吡格药效学及作用机制研究[D].重庆:重庆医科大学,2011. ZHENG XH.Study on the antitumor effects and the lipotoxicity mechanism of TNBG with novel configuration[D].Chongqing:Chongqing Medical University,2011.
[37]ZHENG X,LI W,LAN Z,et al.Antitumour effects of tetrazanbigen against human hepatocellular carcinoma QGY-7701 through inducing lipid accumulation in vitro and in vivo[J].J Pharm Pharmacol,2015,67(11):1593-1602.
[38]刘嫱,陈志琼,梁艳,等.固相萃取-高效液相色谱法测定小鼠血浆中德氮吡格[J].药物分析杂志,2009,29(04):617-619. LIU Q,CHEN ZQ,LIANG Y,et al.SPE-HPLC determination of tetrazanbigen in mice plasma[J].Chinese Journal of Pharmaceutical Analysis,2009,29(04):617-619.
[39]刘嫱,邝少轶,陈志琼,等.静脉注射德氮吡格在小鼠的组织分布及排泄研究[J].中国药理学通报,2013,29(1):142-143. LIU Q,KUANG SY,CHEN ZQ,et al.Biodistribution and excretion of Tetrazanbigen in mice[J].Chinese Pharmacological Bulletin,2013,29(1):142-143.
[40]朱必敏.抗癌新药德氮吡格及其衍生物的构效关系与作用模式[D].重庆:重庆医科大学,2013. ZHU BM.The structure-antivity relationship and interaction of the new antitumor TNBG and its derivatives[D].Chongqing:Chongqing Medical University,2013.
[41]李耀伟.抗肝癌新药德氮吡格衍生物的设计与合成研究[D].重庆:重庆医科大学,2019. LI YW.Design and synthesis of derivatives of anti-hepatocarcinoma drug Tetrazanbigen[D].Chongqing:Chongqing Medical University,2019.
[42]CHEN X,GAN YJ,YU Y,et al.Synthesis and evaluation of new sterol derivatives as potential antitumor agents[J].RSC Adv,2018,8(47):26528-26537.
[43]GAN L,GAN Z,DAN Y,et al.Tetrazanbigen derivatives as peroxisome proliferator-activated receptor gamma (PPARγ) partial agonists:design,synthesis,structure-activity relationship,and anticancer activities[J].J Med Chem,2021,64(2):1018-1036.
[44]GONZLEZ-MAGAA A,BLANCO FJ.Human PCNA structure,function and interactions[J].Biomolecules,2020,10(4):570.
[45]HU X,WAN C,GAN Z,et al.TNBG-5602,a novel derivative of quinoxaline,inhibits liver cancer growth via upregulating peroxisome proliferator-activated receptor γ in vitro and in vivo[J].J Pharm Pharmacol,2019,71(11):1684-1694.
[46]胡雪莲.应用人全基因组siRNA文库筛选并阐述创新型新药TNBG-5602抗肝癌作用的机制[D].重庆:重庆医科大学,2018. HU XL.Study on the antitumor mechanism of TNBG-5602 using a human genomic siRNA library [D].Chongqing:Chongqing Medical University,2018.
[47]SELVAM C,MUTISYA D,PRAKASH S,et al.Therapeutic potential of chemically modified siRNA:Recent trends[J].Chem Biol Drug Des,2017,90(5):665-678.
[48]ELBASHIR S,HARBORTH J,LENDECKEL W,et al.Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells [J].Nature,2001,411(6836):494-498.
[49]HANNON GJ,ROSSI JJ.Unlocking the potential of the human genome with RNA interference[J].Nature,2004,431(7006):371-378.
[50]LI J,YEN C,LIAW D,et al.PTEN,a putative protein tyrosine phosphatase gene mutated in human brain,breast,and prostate cancer[J].Science,1997,275:1943-1947.
[51]HE Y,SUN MM,ZHANG GG,et al.Targeting PI3K/Akt signal transduction for cancer therapy[J].Signal Transduct Target Ther,2021,6(1):425.
[52]WANG J,LI Y,WAN CM,et al.PTEN inhibition leads to the development of resistance to novel isoquinoline derivative TNBG-5602 in human liver cancer cells[J].Am J Cancer Res,2021,11(9):4515-4527.
[53]LI R,ZHOU S,GAN Z,et al.The biological fate of a novel anticancer drug candidate TNBG-5602:Metabolic profile,interaction with CYP450,and pharmacokinetics in rats[J].Molecules,2022,27(8):2594.
[54]但彦肜.新型抗肿瘤德氮吡格衍生物T-1019的药效学及作用机制研究[D].重庆:重庆医科大学,2021. DAN YR.Pharmacodynamices and mechanism of novel antitumor tetrazanbigen derivative T-1019[D].Chongqing:Chongqing Medical University,2021.


National Natural Science Foundation of China(No.30171070,30371632,30772595);国家自然科学基金项目(编号:30171070,30371632,30772595)
Last Update: 2023-05-31