[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.
[2]
Newman, D.J.; Cragg, G.M. Natural products as sources of new drugs over the 30 years from 1981 to 2010. J. Nat. Prod., 2012, 75(3), 311-335.
[3]
Patridge, E.; Gareiss, P.; Kinch, M.S.; Hoyer, D. An analysis of FDA-approved drugs: Natural products and their derivatives. Drug Discov. Today, 2016, 21(2), 204-207.
[4]
Mishra, B.B.; Tiwari, V.K. Natural products: An evolving role in future drug discovery. Eur. J. Med. Chem., 2011, 46(10), 4769-4807.
[5]
Harvey, A.L.; Edrada-Ebel, R.; Quinn, R.J. The re-emergence of natural products for drug discovery in the genomics era. Nat. Rev. Drug Discov., 2015, 14(2), 111-129.
[6]
Katz, L.; Baltz, R.H. Natural product discovery: Past, present, and future. J. Ind. Microbiol. Biot., 2016, 43(2-3), 155-176.
[7]
Weng, Z.Y.; Huang, S.X.; Li, M.L.; Zeng, Y.Q.; Han, Q.B.; Rios, J.L.; Sun, H.D. Isolation of two bioactive ent-Kauranoids from the leaves of Isodon xerophilus. J. Agr. Food Chem., 2007, 55(15), 6039-6043.
[8]
Li, X.; Pu, J.; Jiang, S.; Su, J.; Kong, L.; Mao, B.; Sun, H.; Li, Y. Henryin, an ent-kaurane diterpenoid, inhibits Wnt signaling through interference with β-catenin/TCF4 interaction in colorectal cancer cells. PLoS One, 2013, 8(7), e68525.
[9]
Ma, Y.C.; Su, N.; Shi, X.J.; Zhao, W.; Ke, Y.; Zi, X.; Zhao, N.M.; Qin, Y.H.; Zhao, H.W.; Liu, H.M. Jaridonin-induced G2/M phase arrest in human esophageal cancer cells is caused by reactive oxygen species-dependent Cdc2-tyr15 phosphorylation via ATM-Chk1/2-Cdc25C pathway. Toxicol. Appl. Pharm., 2015, 282(2), 227-236.
[10]
Xu, Y.; Liu, J.; Wu, Y.; Guo, Q.; Sun, H.; Chen, G. Natural products against hematological malignancies and identification of their targets. Sci. China Life Sci., 2015, 58(12), 1191-1201.
[11]
Zhao, Z.; Chen, Y. Oridonin, a promising antitumor natural product in the chemotherapy of hematological malignancies. Curr. Pharm. Biotech., 2014, 15(11), 1083-1092.
[12]
Hsieh, T.C.; Wijeratne, E.K.; Liang, J.Y.; Gunatilaka, A.L.; Wu, J.M. Differential control of growth, cell cycle progression, and expression of NF-kappa B in human breast cancer cells MCF-7, MCF-10A, and MDA-MB-231 by ponicidin and oridonin, diterpenoids from the chinese herb Rabdosia rubescens. Biochem. Bioph. Res. Commun., 2005, 337(1), 224-231.
[13]
Ma, Y.C.; Ke, Y.; Zi, X.; Zhao, W.; Shi, X.J.; Liu, H.M. Jaridonin, a novel ent-kaurene diterpenoid from isodon rubescens, inducing apoptosis via production of reactive oxygen species in esophageal cancer cells. Curr. Cancer Drug Tar., 2013, 13(6), 611-624.
[14]
Liu, X.; Yang, J.; Wang, W.G.; Li, Y.; Wu, J.Z.; Pu, J.X.; Sun, H.D. Diterpene alkaloids with an aza-ent-kaurane skeleton from isodon rubescens. J. Nat. Prod., 2015, 78(2), 196-201.
[15]
Kang, N.; Cao, S.J.; Zhou, Y.; He, H.; Tashiro, S.I.; Onodera, S.; Qiu, F.; Ikejima, T. Inhibition of caspase-9 by oridonin, a diterpenoid isolated from Rabdosia rubescens, augments apoptosis in human laryngeal cancer cells. Int. J. Oncol., 2015, 47(6), 2045-2056.
[16]
Ma, S.; Tan, W.; Du, B.; Liu, W.; Li, W.; Che, D.; Zhang, G. Oridonin effectively reverses cisplatin drug resistance in human ovarian cancer cells via induction of cell apoptosis and inhibition of matrix metalloproteinase expression. Mol. Med. Rep., 2016, 13(4), 3342-3348.
[17]
Ren, C.M.; Li, Y.; Chen, Q.Z.; Zeng, Y.H.; Shao, Y.; Wu, Q.X.; Yuan, S.X.; Yang, J.Q.; Yu, Y.; Wu, K.; He, B.C.; Sun, W.J. Oridonin inhibits the proliferation of human colon cancer cells by upregulating BMP7 to activate p38 MAPK. Oncol. Rep., 2016, 35(5), 2691-2698.
[18]
Ikezoe, T.; Chen, S.S.; Tong, X.J.; Heber, D.; Taguchi, H.; Koeffler, H.P. Oridonin induces growth inhibition and apoptosis of a variety of human cancer cells. Int. J. Oncol., 2003, 23(4), 1187-1193.
[19]
Huang, S.X.; Zhao, Q.S.; Xu, G.; Xiao, W.L.; Li, R.T.; Hou, A.J.; Peng, S.L.; Ding, L.S.; Sun, H.D. ent-kaurane diterpenoids from Isodon albopilosus. J. Nat. Prod., 2005, 68(12), 1758-1762.
[21]
Xu, Z.Z.; Fu, W.B.; Jin, Z.; Guo, P.; Wang, W.F.; Li, J.M. Reactive oxygen species mediate oridonin-induced apoptosis through DNA damage response and activation of JNK pathway in diffuse large B cell lymphoma. Leukemia . Lymphoma, 2016, 57(4), 888-898.
[22]
Xu, W.; Sun, J.; Zhang, T.T.; Ma, B.; Cui, S.M.; Chen, D.W.; He, Z.G. Pharmacokinetic behaviors and oral bioavailability of oridonin in rat plasma. Acta Pharmacol. Sin., 2006, 27(12), 1642-1646.
[23]
Wen, X.U.; Jin, S.U.N.; Tingting, Z.; Bo, M.A.; Dawei, C.; Zhonggui, H.E. Determination of equilibrium solubility of oridonin and its apparent oil/water partition coefficient by HPLC. J. Shenyang Pharm. Univ., 2007, 24(4), 220-222.
[24]
Zhang, X.; Zhang, T.; Lan, Y.; Wu, B.; Shi, Z. Nanosuspensions
containing Oridonin/HP-β-cyclodextrin inclusion complexes for
oral bioavailability enhancement via improved dissolution and
permeability. Aaps Pharmscitech, 2016, 17(2), 400-408.
[25]
Liu, Y.; Zhang, P.; Feng, N.; Zhang, X.; Wu, S.; Zhao, J. Optimization and in situ intestinal absorption of self-microemulsifying drug delivery system of oridonin. Int. J. Pharm., 2009, 365(1-2), 136-142.
[26]
Li, S.; Liu, Y.; Liu, T.; Zhao, L.; Zhao, J.; Feng, N. Development and in-vivo assessment of the bioavailability of oridonin solid dispersions by the gas anti-solvent technique. Int. J. Pharm., 2011, 411(1-2), 172-177.
[27]
Gao, L.; Zhang, D.; Chen, M.; Zheng, T.; Wang, S. Preparation and characterization of an oridonin nanosuspension for solubility and dissolution velocity enhancement. Drug Dev. Ind. Pharm., 2007, 33(12), 1332-1339.
[28]
Ding, Y.; Ding, C.; Ye, N.; Liu, Z.; Wold, E.A.; Chen, H.; Wild, C.; Shen, Q.; Zhou, J. Discovery and development of natural product oridonin-inspired anticancer agents. Eur. J. Med. Chem., 2016, 122, 102-117.
[29]
Chen, R.Y.; Xu, B.; Chen, S.F.; Chen, S.S.; Zhang, T.; Ren, J.; Xu, J. Effect of oridonin-mediated hallmark changes on inflammatory pathways in human pancreatic cancer (BxPC-3) cells. World J. Gastroenterol., 2014, 20(40), 14895-14903.
[30]
Xu, S.; Pei, L.; Li, D.; Yao, H.; Cai, H.; Yao, H.; Wu, X.; Xu, J. Synthesis and antimycobacterial evaluation of natural oridonin and its enmein-type derivatives. Fitoterapia, 2014, 99, 300-306.
[31]
Fujita, E.; Nagao, Y.; Node, M.; Kaneko, K.; Nakazawa, S.; Kuroda, H. Antitumor activity of the Isodon diterpenoids: Structural requirements for the activity. Experientia, 1976, 32(2), 203-206.
[32]
Wang, S.; Yu, L.; Yang, H.; Li, C.; Hui, Z.; Xu, Y.; Zhu, X. Oridonin
attenuates synaptic loss and cognitive deficits in an Aβ-1-42-
induced mouse model of alzheimer's disease. Plos One, 2016, 11(3), //doi.org/10.1371/journal.pone.0151397.
[33]
Zhang, Z.Y.; Daniels, R.; Schluesener, H.J. Oridonin ameliorates neuropathological changes and behavioural deficits in a mouse model of cerebral amyloidosis. J. Cell. Mol. Med., 2013, 17(12), 1566-1576.
[34]
Hu, A.P.; Du, J.M.; Li, J.Y.; Liu, J.W. Oridonin promotes CD4+/CD25+Treg differentiation, modulates Th1/Th2 balance and induces HO-1 in rat splenic lymphocytes. Inflamm. Res., 2008, 57(4), 163-170.
[35]
Liu, J.W.; Yang, F.; Zhang, Y.; Li, J.Y. Studies on the cell-immunosuppressive mechanism of oridonin from Isodon serra. Int. Immunopharmacol., 2007, 7(7), 945-954.
[36]
Zhou, L.; Sun, L.J.; Wu, H.K.; Zhang, L.Z.; Chen, M.C.; Liu, J.W.; Zhong, R.Q. Oridonin ameliorates lupus-like symptoms of MRLlpr/lpr mice by inhibition of B-cell activating factor (BAFF). Eur. J. Pharmacol., 2013, 715(1-3), 230-237.
[37]
Lee, E.J.; Cha, H.J.; Ahn, K.J.; An, I.S.; An, S.; Bae, S. Oridonin exerts protective effects against hydrogen peroxide-induced damage by altering microRNA expression profiles in human dermal fibroblasts. Int. J. Mol. Med., 2013, 32(6), 1345-1354.
[38]
Liu, G.A.; Ding, L.; Yang, Y.; Yang, H.; Yang, Q.M.; Wang, H.Q. Anti-oxidative action of ent-kaurene diterpenoids. Res. Chem. Intermed., 2006, 32(8), 787-794.
[39]
Murayama, C.; Nagao, Y.; Sano, S.; Ochiai, M.; Fuji, K.; Fujita, E.; Mori, T. Effect of oridonin, a Rabdosia diterpenoid, on radiosensitization with misonidazole. Experientia, 1987, 43(11-12), 1221-1223.
[40]
Chen, Q.; Wu, Q. M.; Cheng, J.; Ma, S.L.; Long, H. Study on the
radiosensitization effect of oridonin on esophageal cancer stem
cell. China J. Mod. Med.,, 2012, 29, 014.
[41]
Bohanon, F.J.; Wang, X.F.; Ding, C.Y.; Ding, Y.; Radhakrishnan, G.L.; Rastellini, C.; Zhou, J.; Radhakrishnan, R.S. Oridonin inhibits hepatic stellate cell proliferation and fibrogenesis. J. Surg. Res., 2014, 190(1), 55-63.
[42]
Zang, K.H.; Shao, Y.Y.; Zuo, X.; Rao, Z.; Qin, H.Y. Oridonin alleviates visceral hyperalgesia in a rat model of postinflammatory irritable bowel syndrome: Role of colonic enterochromaffin cell and serotonin availability. J. Med. Food, 2016, 19(6), 586-592.
[43]
Wang, L.X.; Sun, Y.; Chen, C.; Huang, X.Y.; Lin, Q.; Qian, G.Q.; Dong, W.; Chen, Y.F. Effects and mechanism of oridonin on pulmonary hypertension induced by chronic hypoxia-hypercapnia in rats. Chinese . Med. J., 2009, 122(12), 1380-1387.
[44]
Zhen, T.; Wu, C.F.; Liu, P.; Wu, H.Y.; Zhou, G.B.; Lu, Y.; Liu, J.X.; Liang, Y.; Li, K.K.; Wang, Y.Y.; Xie, Y.Y.; He, M.M.; Cao, H.M.; Zhang, W.N.; Chen, L.M.; Petrie, K.; Chen, S.J.; Chen, Z. Targeting of AML1-ETO in t(8;21) leukemia by oridonin generates a tumor suppressor-like protein. Sci. Transl. Med., 2012, 4(127)
[45]
Guo, Y.; Shan, Q.; Gong, Y.; Lin, J.; Yang, X.; Zhou, R. Oridonin in combination with imatinib exerts synergetic anti-leukemia effects in Ph+ acute lymphoblastic leukemia cells in vitro by inhibiting activation of LYN/mTOR signaling pathway. Cancer Biol. Ther., 2012, 13(13), 1244-1254.
[46]
Ming, M.; Sun, F.Y.; Zhang, W.T.; Liu, J.K. Therapeutic effect of oridonin on mice with prostate cancer. Asian Pac. J. Trop. Med., 2016, 9(2), 182-185.
[47]
Ding, C.; Zhang, Y.; Chen, H.; Yang, Z.; Wild, C.; Ye, N.; Ester, C.D.; Xiong, A.; White, M.A.; Shen, Q.; Zhou, J. Oridonin ring A-based diverse constructions of enone functionality: Identification of novel dienone analogues effective for highly aggressive breast cancer by inducing apoptosis. J. Med. Chem., 2013, 56(21), 8814-8825.
[48]
Ding, C.; Wang, L.; Chen, H.; Wild, C.; Ye, N.; Ding, Y.; Wang, T.; White, M.A.; Shen, Q.; Zhou, J. ent-Kaurane-based regio- and stereoselective inverse electron demand hetero-Diels-Alder reactions: synthesis of dihydropyran-fused diterpenoids. Org. Biomol. Chem., 2014, 12(42), 8442-8452.
[49]
Ding, C.; Zhang, Y.; Chen, H.; Yang, Z.; Wild, C.; Chu, L.; Liu, H.; Shen, Q.; Zhou, J. Novel nitrogen-enriched oridonin analogues with thiazole-fused a-ring: protecting group-free synthesis, enhanced anticancer profile, and improved aqueous solubility. J. Med. Chem., 2013, 56(12), 5048-5058.
[50]
Ding, C.; Zhang, Y.; Chen, H.; Wild, C.; Wang, T.; White, M.A.; Shen, Q.; Zhou, J. Overcoming synthetic challenges of oridonin A-ring structural diversification: Regio- and stereoselective installation of azides and 1,2,3-triazoles at the C-1, C-2, or C-3 position. Org. Lett., 2013, 15(14), 3718-3721.
[51]
Wang, L.; Li, D.; Xu, S.; Cai, H.; Yao, H.; Zhang, Y.; Jiang, J.; Xu, J. The conversion of oridonin to spirolactone-type or enmein-type diterpenoid: Synthesis and biological evaluation of ent-6,7-seco-oridonin derivatives as novel potential anticancer agents. Eur. J. Med. Chem., 2012, 52, 242-250.
[52]
Li, D.; Cai, H.; Jiang, B.; Liu, G.; Wang, Y.; Wang, L.; Yao, H.; Wu, X.; Sun, Y.; Xu, J. Synthesis of spirolactone-type diterpenoid derivatives from kaurene-type oridonin with improved antiproliferative effects and their apoptosis-inducing activity in human hepatoma Bel-7402 cells. Eur. J. Med. Chem., 2013, 59, 322-328.
[53]
Li, D.; Xu, S.; Cai, H.; Pei, L.; Zhang, H.; Wang, L.; Yao, H.; Wu, X.; Jiang, J.; Sun, Y.; Xu, J. Enmein-type diterpenoid analogs from natural kaurene-type oridonin: Synthesis and their antitumor biological evaluation. Eur. J. Med. Chem., 2013, 64, 215-221.
[54]
Li, D.; Xu, S.; Cai, H.; Pei, L.; Wang, L.; Wu, X.; Yao, H.; Jiang, J.; Sun, Y.; Xu, J. Library construction and biological evaluation of enmein-type diterpenoid analogues as potential anticancer agents. ChemMedChem, 2013, 8(5), 812-818.
[55]
Xu, J.; Yang, J.; Ran, Q.; Wang, L.; Liu, J.; Wang, Z.; Wu, X.; Hua, W.; Yuan, S.; Zhang, L.; Shen, M.; Ding, Y. Synthesis and biological evaluation of novel 1-O- and 14-O-derivatives of oridonin as potential anticancer drug candidates. Bioorg. Med. Chem. Lett., 2008, 18(16), 4741-4744.
[57]
Wang, L.; Ran, Q.; Li, D.H.; Yao, H.Q.; Zhang, Y.H.; Yuan, S.T.; Zhang, L.Y.; Shen, M.Q.; Xu, J.Y. Synthesis and anti-tumor activity of 14-O-derivatives of natural oridonin. Chin. J. Nat. Med., 2011, 9(3), 194-198.
[58]
Liu, J.; Gao, J. Antitumor activity of components from isondon rubescens (hemsley) H. Hara and their acetyl derivatives predicted by michael addition reaction. Chem. Ind. For. Prod., 2016, 36(1), 27-34.
[59]
Fujita, E.; Nagao, Y.; Kohno, T.; Matsuda, M.; Ozaki, M. Terpenoids.46. anti-tumor activity of acylated oridonin. Chem. Pharm. Bull., 1981, 29(11), 3208-3213.
[60]
Wang, L.; Li, D.; Wang, C.; Zhang, Y.; Xu, J. Recent progress in the development of natural ent-kaurane diterpenoids with anti-tumor activity. Mini Rev. Med. Chem., 2011, 11(10), 910-919.
[61]
Zhang, W.; Huang, Q.; Hua, Z.C. Oridonin: A promising anticancer drug from China. Front. Biol., 2010, 5(6), 540-545.
[62]
Wang, C.; Jiang, L.; Wang, S.; Shi, H.; Wang, J.; Wang, R.; Li, Y.; Dou, Y.; Liu, Y.; Hou, G.; Ke, Y.; Liu, H. The antitumor activity of the novel compound jesridonin on human esophageal carcinoma cells. PLoS One, 2015, 10(6), e0130284.
[63]
Li, D.H.; Wang, L.; Cai, H.; Jiang, B.W.; Zhang, Y.H.; Sun, Y.J.; Xu, J.Y. Synthesis of novel furozan-based nitric oxide-releasing derivatives of 1-oxo-oridonin with anti-proliferative activity. Chin. J. Nat. Med., 2012, 10(6), 471-476.
[64]
Li, D.; Wang, L.; Cai, H.; Zhang, Y.; Xu, J. Synthesis and biological evaluation of novel furozan-based nitric oxide-releasing derivatives of oridonin as potential anti-tumor agents. Molecules, 2012, 17(6), 7556-7568.
[65]
Xu, S.; Wang, G.; Lin, Y.; Zhang, Y.; Pei, L.; Yao, H.; Hu, M.; Qiu, Y.; Huang, Z.; Zhang, Y.; Xu, J. Novel anticancer oridonin derivatives possessing a diazen-1-ium-1,2-diolate nitric oxide donor moiety: Design, synthesis, biological evaluation and nitric oxide release studies. Bioorg. Med. Chem. Lett., 2016, 26(12), 2795-2800.
[66]
Xu, S.; Pei, L.; Wang, C.; Zhang, Y.K.; Li, D.; Yao, H.; Wu, X.; Chen, Z.S.; Sun, Y.; Xu, J. Novel hybrids of natural oridonin-bearing nitrogen mustards as potential anticancer drug candidates. ACS Med. Chem. Lett., 2014, 5(7), 797-808.
[67]
Xu, S.; Li, D.; Pei, L.; Yao, H.; Wang, C.; Cai, H.; Yao, H.; Wu, X.; Xu, J. Design, synthesis and antimycobacterial activity evaluation of natural oridonin derivatives. Bioorg. Med. Chem. Lett., 2014, 24(13), 2811-2814.
[68]
Bohanon, F.J.; Wang, X.; Graham, B.M.; Ding, C.; Ding, Y.; Radhakrishnan, G.L.; Rastellini, C.; Zhou, J.; Radhakrishnan, R.S. Enhanced effects of novel oridonin analog CYD0682 for hepatic fibrosis. J. Surg. Res., 2015, 199(2), 441-449.
[69]
Bohanon, F.J.; Wang, X.; Graham, B.M.; Prasai, A.; Vasudevan, S.J.; Ding, C.; Ding, Y.; Radhakrishnan, G.L.; Rastellini, C.; Zhou, J.; Radhakrishnan, R.S. Enhanced anti-fibrogenic effects of novel oridonin derivative CYD0692 in hepatic stellate cells. Mol. Cell. Biochem., 2015, 410(1-2), 293-300.
[70]
Qiu, Z.; Chen, Y.; Sun, P.; Wu, G. New L-alanine-(14-oridonin)
ester trifluoroacetate salt useful for treating e.g. oesophageal cancer,
gastric cancer, primary liver cancer, pancreatic cancer, colorectal
cancer, bladder cancer and acute myeloid leukemia.
CN104017000-A, 03 Sep 2014 C07D-493/08 201509.
[71]
Liu, Q.Q.; Wang, H.L.; Chen, K.; Wang, S.B.; Xu, Y.; Ye, Q.; Sun, Y.W. Oridonin derivative ameliorates experimental colitis by inhibiting activated T-cells and translocation of nuclear factor-kappa B. J. Digest. Dis., 2016, 17(2), 104-112.
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