Login Register Cart 0
Generic placeholder image

当代肿瘤药物靶点

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in English
Research Article

6-羟基黄嘌呤二烯叠氮衍生物的合成及细胞毒活性

卷 20, 期 9, 2020

页: [666 - 674] 页: 9

弟呕挨: 10.2174/1568009620999200421200338

价格: $65

摘要

背景：已经合成并通过NMR光谱仪鉴定并合成了6-羟基黄嘌呤二烯的eremophilane系列的倍半萜内酯与氢化杂志（哌啶和哌嗪）的共轭物。 目的：从植物土木香（Inula helenium L）中提取具有异常骨架“ 6-羟基黄嘌呤二烯”的内酯，并用NMR光谱仪鉴定各种物种。 方法：研究了A549，HCT116，RD和Jurkat等不同肿瘤系的细胞毒性，线粒体和抗氧化活性，并确定了可能的机制。 结果：结果表明，最有效的化合物是IIIi，对RD细胞具有最高的细胞毒性（IC50 25.23} 0.04μM），使线粒体膜去极化，并且是一种有效的抗氧化剂（IC50抑制LP 10.68} 3.21μM），没有任何对健康细胞的毒副作用。 结论：倍半萜烯内酯6-羟基黄嘌呤二烯III与氢化叠氮的结合可能有助于设计潜在的有前途的抗癌药物。

关键词: 6-羟基黄嘌呤二烯，叠氮，细胞毒性，线粒体，细胞凋亡，抗氧化剂，抗癌药。

« Previous Next »
图形摘要

[1]
Newman, D.J.; Cragg, G.M. Natural products as sources of new drugs from 1981 to 2014. J. Nat. Prod., 2016, 79(3), 629-661.
[http://dx.doi.org/10.1021/acs.jnatprod.5b01055] [PMID: 26852623]
[2]
Grothaus, P.G.; Cragg, G.M.; Newman, D.J. Plant natural products in anticancer drug discovery. Curr. Org. Chem., 2010, 14, 1781-1791.
[http://dx.doi.org/10.2174/138527210792927708]
[3]
Dandawate, P.R.; Subramaniam, D.; Jensen, R.A.; Anant, S. Targeting cancer stem cells and signaling pathways by phytochemicals: Novel approach for breast cancer therapy. Semin. Cancer Biol., 2016, 40-41, 192-208.
[http://dx.doi.org/10.1016/j.semcancer.2016.09.001] [PMID: 27609747]
[4]
Kreuger, M.R.; Grootjans, S.; Biavatti, M.W.; Vandenabeele, P.; D’Herde, K. Sesquiterpene lactones as drugs with multiple targets in cancer treatment: focus on parthenolide. Anticancer Drugs, 2012, 23(9), 883-896.
[http://dx.doi.org/10.1097/CAD.0b013e328356cad9] [PMID: 22797176]
[5]
Gach, K.; Janecka, A. α-Methylene-γ-lactones as a novel class of anti-leukemic agents. Anticancer. Agents Med. Chem., 2014, 14(5), 688-694.
[http://dx.doi.org/10.2174/1871520614666140313095010] [PMID: 24628266]
[6]
Siveen, K.S.; Uddin, S.; Mohammad, R.M. Targeting acute myeloid leukemia stem cell signaling by natural products. Mol. Cancer, 2017, 16(1), 13.
[http://dx.doi.org/10.1186/s12943-016-0571-x] [PMID: 28137265]
[7]
Merfort, I. Perspectives on sesquiterpene lactones in inflammation and cancer. Curr. Drug Targets, 2011, 12(11), 1560-1573.
[http://dx.doi.org/10.2174/138945011798109437] [PMID: 21561425]
[8]
Harvey, A.L. Medicines from nature: Are natural products still relevant to drug discovery? Trends Pharmacol. Sci., 1999, 20(5), 196-198.
[http://dx.doi.org/10.1016/S0165-6147(99)01346-2] [PMID: 10354614]
[9]
Fraga, B.M. Natural sesquiterpenoids. Nat. Prod. Rep., 2006, 23(6), 943-972.
[http://dx.doi.org/10.1039/b507870a] [PMID: 17119641]
[10]
Ghantous, A.; Gali-Muhtasib, H.; Vuorela, H.; Saliba, N.A.; Darwiche, N. What made sesquiterpene lactones reach cancer clinical trials? Drug Discov. Today, 2010, 15(15-16), 668-678.
[http://dx.doi.org/10.1016/j.drudis.2010.06.002] [PMID: 20541036]
[11]
da Silva Castro, E.; Alves Antunes, L.A.; Revoredo Lobo, J.F.; Ratcliffe, N.A.; Borges, R.M.; Rocha, L.; Burth, P.; Fonte Amorim, L.M. Antileukemic properties of sesquiterpene lactones: A systematic review. Anticancer. Agents Med. Chem., 2018, 18(3), 323-334.
[http://dx.doi.org/10.2174/1871520617666170918130126] [PMID: 28925880]
[12]
Klochkov, S.G.; Afanas’eva, S.V.; Pushin, A.N. Acidic isomerization of alantolactone derivatives. Chem. Nat. Compd., 2006, 42, 400-406.
[http://dx.doi.org/10.1007/s10600-006-0166-7]
[13]
Seaman, F.C.; Fischer, N.H.; Stuessy, T.F. Systematic implications of sesquiterpene lactones in the subtribe Melampodiinae. Biochem. Syst. Ecol., 1980, 8, 263-271.
[http://dx.doi.org/10.1016/0305-1978(80)90057-5]
[14]
Rejmund, M.; Mrozek-Wilczkiewicz, A.; Malarz, K.; Pyrkosz-Bulska, M.; Gajcy, K.; Sajewicz, M.; Musiol, R.; Polanski, J. Piperazinyl fragment improves anticancer activity of Triapine. PLoS One, 2018, 13(4)e0188767
[http://dx.doi.org/10.1371/journal.pone.0188767] [PMID: 29652894]
[15]
Klochkov, S.G.; Ananyev, I.V.; Pukhov, S.A.; Afanasyeva, S.V. Stereochemistry of the aza-michael reaction with natural alantolactones. Chem. Heterocycl. Compd., 2012, 48, 698.
[http://dx.doi.org/10.1007/s10593-012-1047-6]
[16]
Klochkov, S.G.; Romanova, A.A.; Anan, I.V.; Pukhov, S.A.; Afanas, S.V. Afanasieva synthesis and structure of (3R,3aR,4S,4aR,5S,9aR)-4-Hydroxy-4a,5-Dimethyl-3-[4-(4-Fluorophenyl)-Piperazino]Methyl-3a,4,4a,5,6,7,9,9a-Octahydronaphtho [2,3-b]Furan-2(3H)-. One. Chem. Nat. Compd., 2018, 54, 1146-1148.
[http://dx.doi.org/10.1007/s10600-018-2576-8]
[17]
Zamzami, N.; Kroemer, G. The mitochondrion in apoptosis: How Pandora’s box opens. Nat. Rev. Mol. Cell Biol., 2001, 2(1), 67-71.
[http://dx.doi.org/10.1038/35048073] [PMID: 11413468]
[18]
Michelakis, E.D.; Webster, L.; Mackey, J.R. Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer. Br. J. Cancer, 2008, 99(7), 989-994.
[http://dx.doi.org/10.1038/sj.bjc.6604554] [PMID: 18766181]
[19]
Zhang, Y.; Bao, Y.L.; Wu, Y.; Yu, C.L.; Huang, Y.X.; Sun, Y.; Zheng, L.H.; Li, Y.X. Alantolactone induces apoptosis in RKO cells through the generation of reactive oxygen species and the mitochondrial pathway. Mol. Med. Rep., 2013, 8(4), 967-972.
[http://dx.doi.org/10.3892/mmr.2013.1640] [PMID: 23970102]
[20]
Bonner, M.Y.; Arbiser, J.L. The antioxidant paradox: What are antioxidants and how should they be used in a therapeutic context for cancer. Future Med. Chem., 2014, 6(12), 1413-1422.
[http://dx.doi.org/10.4155/fmc.14.86] [PMID: 25329197]
[21]
Halliwell, B.; Gutteridge, J.M.C. Free Radicals in Biology and Medicine, 3rd ed; Oxford University Press: Oxford, 1999.
[22]
Mosmann, T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Methods, 1983, 65(1-2), 55-63.
[http://dx.doi.org/10.1016/0022-1759(83)90303-4] [PMID: 6606682]
[23]
Präbst, K.; Engelhardt, H.; Ringgeler, S.; Hübner, H. Basic Colorimetric Proliferation Assays: MTT, WST, and Resazurin. Methods Mol. Biol., 2017, 1601, 1-17.
[http://dx.doi.org/10.1007/978-1-4939-6960-9_1] [PMID: 28470513]
[24]
Akerman, K.E.; Wikström, M.K. Safranine as a probe of the mitochondrial membrane potential. FEBS Lett., 1976, 68(2), 191-197.
[http://dx.doi.org/10.1016/0014-5793(76)80434-6] [PMID: 976474]
[25]
Chowdhury, S.R.; Djordjevic, J.; Albensi, B.C.; Fernyhough, P. Simultaneous evaluation of substrate-dependent oxygen consumption rates and mitochondrial membrane potential by TMRM and safranin in cortical mitochondria. Biosci. Rep., 2015, 36(1), e00286-e00286.
[http://dx.doi.org/10.1042/BSR20150244] [PMID: 26647379]
[26]
Gornall, A.G.; Bardawill, C.J.; David, M.M. Determination of serum proteins by means of the biuret reaction. J. Biol. Chem., 1949, 177(2), 751-766.
[PMID: 18110453]
[27]
Neganova, M.E.; Klochkov, S.G.; Petrova, L.N.; Shevtsova, E.F.; Afanasieva, S.V.; Chudinova, E.S.; Fisenko, V.P.; Bachurin, S.O.; Barreto, G.E.; Aliev, G. Securinine derivatives as potential anti-amyloid therapeutic approach. CNS Neurol. Disord. Drug Targets, 2017, 16(3), 351-355.
[http://dx.doi.org/10.2174/1871527315666161107090525] [PMID: 27823572]

Rights & Permissions Print Cite
Article Metrics
14
© 2025 Bentham Science Publishers | Privacy Policy