靶向G4-DNA的抗肿瘤制剂研究进展
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摘要
根据世界卫生组织的统计,恶性肿瘤已成为导致人类死亡的第二位疾病,严重威胁着人类的健康和生命。铂类抗肿瘤药物是临床上主要的抗癌药物。然而,铂类金属药物在临床上具有严重的不良反应,如肾毒性,骨髓毒性,耳毒性,外周神经毒性,催吐作用和耐药性。高效、低毒的抗肿瘤药物是目前研究的热点。目前,针对各种新靶点的药物已被广泛研究,其中,靶向G4-DNA抑制端粒酶的小分子化合物是一个研究热点,具有良好的应用前景。本文作者就这方面的研究进展进行综述。
According to the statistics of the World Health Organization, malignant tumors have become the second disease leading to human death, which seriously threatens human health and life. Platinum anticancer drugs are the main anticancer drugs in clinic. However, platinum metal drugs have serious adverse reactions in clinic, such as nephrotoxicity, bone marrow toxicity, ototoxicity, peripheral neurotoxicity, emetic effect and drug resistance. Efficient, low-toxic anti-tumor drugs are currently the focus of research. At present, drugs targeting various new targets have been extensively studied. Among them, the small molecule compound targeting G4-DNA to inhibit telomerase is a research hotspot and has a good application prospect. The authors review the progress of research in this area.
According to the statistics of the World Health Organization, malignant tumors have become the second disease leading to human death, which seriously threatens human health and life. Platinum anticancer drugs are the main anticancer drugs in clinic. However, platinum metal drugs have serious adverse reactions in clinic, such as nephrotoxicity, bone marrow toxicity, ototoxicity, peripheral neurotoxicity, emetic effect and drug resistance. Efficient, low-toxic anti-tumor drugs are currently the focus of research. At present, drugs targeting various new targets have been extensively studied. Among them, the small molecule compound targeting G4-DNA to inhibit telomerase is a research hotspot and has a good application prospect. The authors review the progress of research in this area.
引文
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[22] WU P,MA D L,LEUNG C H,et al.Stabilization of G-Quadruplex DNA with platinum(II)schiff base complexes:luminescent probe and down-regulation of c-myc oncogene expression[J].Chem Eur J,2009,15(47):13008-13021.
[23] KIELTYKA R,ENGLEBIENNE P,FAKHOURY J,et al.A platinum supramolecular square as an effective G-quadruplex binder and telomerase inhibitor[J].J Am Chem Soc,2008,130(31):10040-10041.
[24] ZHENG X H,CHEN H Y,TONG M L,et al.Platinum squares with high selectivity and affinity for human telomeric G-quadruplexes[J].Chem Commun,2012,48(61):7607-7609.
[25] CHEN Z F,QIN Q P,QIN J L,et al.Stabilization of G-quadruplex DNA,inhibition of telomerase activityand tumor cell apoptosis by organoplatinum(II)complexes with oxoisoaporphine[J].J Med Chem,2015,58(5):2159-2179.
[26] QIAN C,YI L,EVA F,et al.G-quadruplex DNA targeted metal complexes acting as potential anticancer drugs[J].Inorg Chem Front,2017,4(1):10-32.
[27] 黄竹娟,苏宁,吴绍锋,等.靶向端粒G4-DNA手性钌配合物的抗肿瘤活性研究[J].天津中医药大学学报,2016,35(2):109-113.
[28] 陈兰美,李国栋,彭发,等.钌配合物[Ru(MeIm)4(dpq)]2+与G4-DNADNA的相互作用及抗肿瘤活性[J].广东药学院学报,2015,33(2):152-156。
[29] MONSEN ROBERT O,TRENT JOHN O.G-quadruplex virtual drug screening:a review[J].Biochemie,2018(152):134-148.
[30] 王华华,朱钰,孙颖,等.基于端粒G4-DNA受体构建具有抗肿瘤功效的药效团模型[J].计算机与应用化学,2016,33(3):369-372.
[2] SEKARAN V,SOARES J,JARSTFER M B.Telomere maintenance as a target for drug discovery[J].J Med Chem,2014,57:521-538.
[3] PASQUALE Z,CHIARA C,SIMONA A,et al.Intragenic G-quadruplex structure formed in the human CD133 and its biological and translational relevance[J].Nucleic Acids Res,2016,44(4):1579-1590.
[4] MARO S D,ZIZZA P,SALVATI E,et al.Shading the TRF2 recruiting function:a new horizon in drug development[J].J Am Chem Soc,2014,136(48):16708-16711.
[5] WU G H,YANG D Z.Novel loop interactions within a parallel-stranded G-quadruplex formed in the human BCL-2 proximal promoter [J].Cancer Res,2017,77(13):5225-5225.
[6] YUAN L,TIAN T,CHEN Y,et al.Existence of G-quadruplex structures in promoter region of oncogenes confirmed by G-quadruplex DNA cross-linking strategy[J].Sci Rep,2013,6(3):1811.
[7] BIFFI G,DI ANTONIO M,TANNAHILL D,et al.Visualization and selective chemical targeting of RNA G-quadruplex structures in the cytoplasm of human cells[J].Nat Chem,2014,6(1):75-80.
[8] ZAMIRI B,REDDY K,MACGREGOR R B,et al.TMPyP4 porphyrin distorts RNA G-quadruplex structures of the disease-associated r(GGGGCC)n repeat of the C9 or f72 gene and blocks interaction of RNA-binding proteins[J].J Bio Chem,2014,289(8):4653-4659.
[9] GUO J,LI Z,WANG A,et al.Three new phenolic compounds from the lichen thamnolia vermicularis and their antiproliferative effects in prostate cancer cells[J].Planta Med,2011,77(18):2042-2046.
[10] CHANQENET-BARRET P,GUSTAVSSON T,MARKOVITSI D,et al.Ultrafast electron transfer in complexes of doxorubicin with human telomeric G-Quadruplexes and GC duplexes probed by femtosecond fluorescence spectroscopy[J].Chemphyschem,2016,17(9):1264-1272.
[11] MICCO M,COLLIE G W,DALE A G,et al.Structure-based design and evaluation of naphthalene diimide G-quadruplex ligands as telomere targeting agents in pancreatic cancer cells[J].J Med Chem,2013,56(7):2959-2974.
[12] MA Y,OU T M,TAN J H,et al.Quinolino-benzo-[5,6]-dihydroisoquindolium compounds derived from berberine:a new class of highly selective ligands for G-quadruplex DNA in c-myc oncogene[J].Eur J Med Chem,2011,46(5):1906-1913.
[13] COGOI S,SHCHEKOTIKHIN A E,MEMBRINO A,et al.Guanidino anthrathiophenediones as G-quadruplex binders:uptake,intracellular localizationand anti-Harvey-Ras gene activity in bladder cancer cells[J].J Med Chem,2013,56(7):2764-2778.
[14] LIU H Y,CHEN A C,YIN Q K,et al.New disubstituted quindoline derivatives inhibiting Burkitt’s lymphoma cell proliferation by impeding c-myc transcription[J].J Med Chem,2017,60(13):5438-5454.
[15] SUNTHARALINGAM K,WHITE A J P,VILAR R.Synthesis,structural characterization,and quadruplex DNA binding studies of platinum(II)-terpyridine complexes[J].Inorg Chem,2009,48(19):9427-9435.
[16] ZOU H H,WANG L,LONG Z X,et al.Preparation of 4-([2,2′:6′,2″-terpyridin]-4′-yl)-N,N-diethylanilineNiII and PtII complexes and exploration of their in vitro cytotoxic activities[J].Eur J Med Chem,2016(108):1-12.
[17] MERLE P,GUEUGNEAU M,TEULADE-FICHOU M P,et al.Highly efficient radiosensitization of human glioblastoma and lung cancer cells by a G-quadruplex DNA binding compound[J].Sci Rep,2015,5(1),16255.
[18] BERTRAND H,BOMBARD S,MONCHAUD D,et al.Exclusive platination of loop adenines in the human telomeric G-quadruplex[J].Org Biomol Chem,2009,7(14):2864-2871.
[19] REED J E,NEIDLE S,VILAR R.Stabilisation of human telomeric quadruplex DNA and inhibition of telomerase by a platinum-phenanthroline complex[J].Chem Commun,2007(42):4366-4368.
[20] MA D L,CHE C M,YAN S C.Platinum(II)complexes with dipyridophenazine ligands as human telomerase inhibitors and luminescent probes for G-quadruplex DNA[J].J Am Chem Soc,2008,131(5):1835-1846.
[21] KIELTYKA R,FAKHOURY J,MOITESSIER N,et al.Platinum phenanthroimidazole complexes as G-Quadruplex DNA selective binders[J].Chem Eur J,2008,14(4):1145-1154.
[22] WU P,MA D L,LEUNG C H,et al.Stabilization of G-Quadruplex DNA with platinum(II)schiff base complexes:luminescent probe and down-regulation of c-myc oncogene expression[J].Chem Eur J,2009,15(47):13008-13021.
[23] KIELTYKA R,ENGLEBIENNE P,FAKHOURY J,et al.A platinum supramolecular square as an effective G-quadruplex binder and telomerase inhibitor[J].J Am Chem Soc,2008,130(31):10040-10041.
[24] ZHENG X H,CHEN H Y,TONG M L,et al.Platinum squares with high selectivity and affinity for human telomeric G-quadruplexes[J].Chem Commun,2012,48(61):7607-7609.
[25] CHEN Z F,QIN Q P,QIN J L,et al.Stabilization of G-quadruplex DNA,inhibition of telomerase activityand tumor cell apoptosis by organoplatinum(II)complexes with oxoisoaporphine[J].J Med Chem,2015,58(5):2159-2179.
[26] QIAN C,YI L,EVA F,et al.G-quadruplex DNA targeted metal complexes acting as potential anticancer drugs[J].Inorg Chem Front,2017,4(1):10-32.
[27] 黄竹娟,苏宁,吴绍锋,等.靶向端粒G4-DNA手性钌配合物的抗肿瘤活性研究[J].天津中医药大学学报,2016,35(2):109-113.
[28] 陈兰美,李国栋,彭发,等.钌配合物[Ru(MeIm)4(dpq)]2+与G4-DNADNA的相互作用及抗肿瘤活性[J].广东药学院学报,2015,33(2):152-156。
[29] MONSEN ROBERT O,TRENT JOHN O.G-quadruplex virtual drug screening:a review[J].Biochemie,2018(152):134-148.
[30] 王华华,朱钰,孙颖,等.基于端粒G4-DNA受体构建具有抗肿瘤功效的药效团模型[J].计算机与应用化学,2016,33(3):369-372.