2-氰基-3, 12-二氧齐墩果烷-1, 9(11)-二烯-28-酸及其类似物的结构修饰研究进展

刘芳, 曾光尧, 郭虹, 周应军*

中国药学杂志 ›› 2014, Vol. 49 ›› Issue (3) : 174-179.

PDF(1205 KB)
PDF(1205 KB)
中国药学杂志 ›› 2014, Vol. 49 ›› Issue (3) : 174-179. DOI: 10.11669/cpj.2014.03.003
综 述

2-氰基-3, 12-二氧齐墩果烷-1, 9(11)-二烯-28-酸及其类似物的结构修饰研究进展

  • 刘芳, 曾光尧, 郭虹, 周应军*
作者信息 +

Advances in the Structural Modification Study of CDDO and Its Derivatives

  • LIU Fang, ZENG Guang-yao, GUO Hong, ZHOU Ying-jun*
Author information +
文章历史 +

摘要

目的 综述2-氰基-3, 12-二氧齐墩果烷-1, 9(11)-二烯-28-酸(CDDO)的合成及其衍生物的A、C环, C-2和C-17位等位置的结构修饰及构效关系。方法 以近年来该领域的国内外文献为基础, 对2-氰基-3, 12-二氧齐墩果烷-1, 9(11)-二烯-28-酸及其衍生物的构效关系进行分析和总结。结果与结论 2-氰基-3, 12-二氧齐墩果烷-1, 9(11)-二烯-28-酸及其类似物构效关系的研究, 有助于我们更好地利用2-氰基-3, 12-二氧齐墩果烷-1, 9(11)-二烯-28-酸及其类似物, 并设计合成出活性和选择性更高的药物。

Abstract

OBJECTIVE To systematically summarize studies on the synthesis of 2-cyano-3, 12-dioxoolean-l, 9-dien-28-oic acid (CDDO), structural modification and structure-activity relationship(SAR) of CDDO and its derivatives in the positions of A, C rings, C-2, C-17 and others. METHODS Based on the newest research reports at home and abroad, the SARs of CDDO and its derivatives were analyzed and summarized. RESULTS AND CONCLUSION SAR studies of CDDO and its derivatives can help us use them as references for the development of drugs with better actitivity and selectivity.

关键词

2-氰基-3 / 12-二氧齐墩果烷-1 / 9(11)-二烯-28-酸(CDDO) / 衍生物 / 结构修饰 / 构效关系

Key words

2-cyano-3, 12-dioxoolean-l, 9-dien-28-oic acid(CDDO) / derivatives / structural modification / structure-activity relationship

引用本文

导出引用
刘芳, 曾光尧, 郭虹, 周应军*. 2-氰基-3, 12-二氧齐墩果烷-1, 9(11)-二烯-28-酸及其类似物的结构修饰研究进展[J]. 中国药学杂志, 2014, 49(3): 174-179 https://doi.org/10.11669/cpj.2014.03.003
LIU Fang, ZENG Guang-yao, GUO Hong, ZHOU Ying-jun*. Advances in the Structural Modification Study of CDDO and Its Derivatives[J]. Chinese Pharmaceutical Journal, 2014, 49(3): 174-179 https://doi.org/10.11669/cpj.2014.03.003
中图分类号: R97   

参考文献

TANG F, LI H D. Dispersion of oleanolic acid drop pills and its evaluation in vitro.Chin Pharm J(中国药学杂志), 2008, 43(15):1167-1169. HONDA T, HONDA Y, FAVALORO F J, et al. A novel dicyanotriterpenoid, 2-cyano-3, 12-dioxooleana-1, 9(11)-dien-28-onitrile, active at picomolar concentrations for inhibition of nitric oxide production. Bioorg Med Chem Lett, 2002, 12(7):1027-1030. SUH N, WANG Y P, HONDA T, et al. A novel synthetic oleanane triterpenoid, 2-cyano-3, 12-dioxoolean-1, 9-dien-28-oic acid, with potent differentiating, antiproliferative, and anti-inflammatory activity.Cancer Res, 1999, 59:336-341. LIBY K, HOCK T, YORE M M, et al. The synthetic triterpenoids, CDDO and CDDO-imidazolide, are potent inducers of heme oxygenase-1 and Nrf2/ARE signaling. Cancer Res, 2005, 65(11):4789-4798. DINKOVA-KOSTOVA A T, LIBY K T, STEPHENSON K K, et al. Extremely potent triterpenoid inducers of the phase 2 response: Correlations of protection against oxidant and inflammatory stress. Proc Natl Acad Sci USA, 2005, 22;102(12):4584-4589. WANG Y, PORTER W W, SUH N, et al. A synthetic triterpenoid, 2-cyano-3, 12-dioxooleana-1, 9-dien-28-oic acid(CDDO), is a ligand for the peroxisome proliferator-activated receptor gamma. Mol Endocrinol, 2000, 14(10):1550-1556. ITO Y, PANDEY P, PLACE A, et al. The novel triterpenoid 2-cyano-3, 12-dioxoolean-1, 9-dien-28-oic acid induces apoptosis of human myeloid leukemia cells by a caspase-8-dependent mechanism. Cell Growth Differ, 2000, 11(5):261-267. KONOPLEVA M, TSAO T, ESTROV Z, et al. The synthetic triterpenoid 2-cyano-3, 12-dioxooleana-1, 9-dien-28-oic acid induces caspase-dependent and -independent apoptosis in acute myelogenous leukemia. Cancer Res, 2004, 64(21):7927-7935. KIM K B, LOTAN R, YUE P, et al. Identification of a novel synthetic triterpenoid, methyl-2-cyano-3, 12-dioxooleana-1, 9-dien-28-oate, that potently induces caspase-mediated apoptosis in human lung cancer cells. Mol Cancer Ther, 2002, 1(3):177-184. ITO Y, PANDEY P, SPORN M B, et al. The novel triterpenoid CDDO induces apoptosis and differentiation of human osteosarcoma cells by a caspase-8 dependent mechanism. Mol Pharmacol, 2001, 59(5):1094-1099. PEDERSEN I M, KITADA S, SCHIMMER A, et al. The triterpenoid CDDO induces apoptosis in refractory CLL B cells. Blood, 2002, 100(8):2965-2972. SPORN M B, LIBY K T, YORE M M. New synthetic triterpenoids: Potent agents for prevention and treatment of tissue injury caused by inflammatory and oxidative stress. J Nat Prod, 2011, 74(3):537-545. HONDA T, ROUNDS B V, GRIBBLE G W, et al. Design and synthesis of 2-cyano-3, 12-dioxoolean-1, 9-dien-28-oic acid, a novel and highly active inhibitor of nitric oxide production in mouse macrophages. Bioorg Med Chem Lett, 1998, 8(19):2711-2714. COUCH R D, BROWNING R G, HONDA T, et al. Studies on the reactivity of CDDO, a promising new chemopreventive and chemotherapeutic agent: Implications for a molecular mechanism of action. Bioorg Med Chem Lett, 2005, 15(9):2215-2219. ALABRAN J L, CHEUK A, LIBY K, et al. Human neuroblastoma cells rapidly enter cell cycle arrest and apoptosis following exposure to C-28 derivatives of the synthetic triterpenoid CDDO. Cancer Biol Ther, 2008, 7(5):709-717. YORE M M, LIBY K T, HONDA T, et al. The synthetic triterpenoid 1-imidazole blocks nuclear factor-kappaB activation through direct inhibition of IkappaB kinase beta. Mol Cancer Ther, 2006, 5(12):3232-3239. ZHENG S, SANTOSH L Y, DAVID E, et al. Synthesis, chemical reactivity as michael acceptors, and biological potency of monocyclic cyanoenones, novel and highly potent anti-inflammatory and cytoprotective agents. J Med Chem, 2012, 55(10):4837-4846. NEYMOTIN A, CALINGASAN N Y, WILLE E, et al. Neuroprotective effect of Nrf2/ARE activators, CDDO ethylamide and CDDO trifluoroethylamide, in a mouse model of amyotrophic lateral sclerosis. Free Radic Biol Med, 2011, 51(1):88-96. ZHENG S, SANTOSH L Y, DAVID E, et al. Synthesis, chemical reactivity as michael acceptors, and biological potency of monocyclic cyanoenones, novel and highly potent anti-inflammatory and cytoprotective agents. J Med Chem, 2012, 55(10):4837-4846. PERGOLA P E, RASKIN P, TOTO R D, et al. Bardoxolone methyl and kidney function in CKD with type 2 diabetes. N Enql J Med, 2011, 365(4):327-336. FU L, GRIBBLE G W. Efficient and scalable synthesis of bardoxolone methyl(CDDO-methyl ester) . Org Lett, 2013, 7(15):1622-1625. CHADALAPAKA G, JUTOORU I, MCALEES A, et al. Structure-dependent inhibition of bladder and pancreatic cancer cell growth by 2-substituted glycyrrhetinic and ursolic acid derivatives. Bioorg Med Chem Lett, 2008, 18(8):2633-2639. HONDA T, SUNDARARAJAN C, YOSHIZAWA H, et al. Novel tricyclic compounds having acetylene groups at C-8a and cyano enones in rings A and C: Highly potent anti-inflammatory and cytoprotective agents. J Med Chem, 2007, 50(8):1731-1734. LIBY K, YORE M M, ROEBUCK B D, et al. A novel acetylenic tricyclic bis-(cyano enone) potently induces phase 2 cytoprotective pathways and blocks liver carcinogenesis induced by aflatoxin. Cancer Res, 2008, 68(16):6727-6733. ZHAO Q S, CONG Y W. Michael reaction accept or molecules in chemical biology .Prog Chem(化学进展), 2007, 19(12):1972-1976. HONDA T, YOSHIZAWA H, SUNDARARAJAN C, et al. Tricyclic compounds containing nonenolizable cyano enones. A novel class of highly potent anti-inflammatory and cytoprotective agents. J Med Chem, 2011, 54(6):1762-1778. ZHENG S, SANTOSH L Y, DAVID E, et al. Synthesis, chemical reactivity as michael acceptors, and biological potency of monocyclic cyanoenones, novel and highly potent anti-inflammatory and cytoprotective agents. J Med Chem, 2012, 55(10):4837-4846. FINLAY H J, HONDA T, GRIBBLE G W, et al. Novel A-ring cleaved analogs of oleanolic and ursolic acids which affect growth regulation in NRP.152 prostate cells. Bioorg Med Chem Lett, 1997, 7(13):1769-1772. HONDA T, DINKOVA-KOSTOVA A T, DAVID E, et al. Synthesis and biological evaluation of 1--4-ethynylimidazole. A novel and highly potent anti-inflammatory and cytoprotective agent. Bioorg Med Chem Lett, 2011, 21(8):2188-2191. DINKOVA-KOSTOVA A T, JENKINS S N, WEHAGE S L, et al. A dicyanotriterpenoid induces cytoprotective enzymes and reduces multiplicity of skin tumors in UV-irradiated mice. Biochem Biophys Res Commun, 2008, 367(4):859-865. HONDA T, PADEGIMAS E M, DAVID E, et al. 2-Cyano-3, 10-dioxooleana-1, 9(11)-dien-28-oic acid anhydride. A novel and highly potent anti-inflammatory and cytoprotective agent. Bioorg Med Chem Lett, 2010, 20(7):2275-2278. ZHAO J, ZHANG W D. Adcance in multiple target biology systems and multi-component drugs . Chin Pharm J(中国药学杂志), 2010, 45(15):1121-1126.
PDF(1205 KB)

44

Accesses

0

Citation

Detail

段落导航
相关文章

/