Journal of Chinese Pharmaceutical Sciences ›› 2020, Vol. 29 ›› Issue (7): 443-454.DOI: 10.5246/jcps.2020.07.042
• Review • Next Articles
Eric Wei Chiang Chan1*, Oi Yoon Michelle Soo1, Yong Hui Tan1, Siu Kuin Wong2, Hung Tuck Chan3
>
>Received:2020-03-14
Revised:2020-04-20
Online:2020-07-31
Published:2020-05-12
Contact:
Tel.: +60-3-9101-8880, E-mail: chanwc@ucsiuniversity.edu.my, erchan@yahoo.com
About author:Dr. Eric Chan, Associate Professor at the Faculty of Applied Sciences, UCSI University, Kuala Lumpur, Malaysia, obtained his PhD (Natural Product Chemistry) from Monash University Malaysia in 2009. To date, Dr. Eric Chan has 88 publications in international refereed journals with 66 (6 in JCPS) as the lead author. His publications have received more than 1450 citations in Scopus and 3000 citations in Google Scholar. He was one of the Top 5 Competitors of the Elsevier Green and Sustainable Chemistry Challenge 2015, out of 500 proposals submitted globally. In April 2016, he presented his proposal at the Green and Sustainable Chemistry Conference in Berlin, Germany. In the same month, he was awarded the Promising Researcher Award by UCSI University.
CLC Number:
Supporting:
Eric Wei Chiang Chan, Oi Yoon Michelle Soo, Yong Hui Tan, Siu Kuin Wong, Hung Tuck Chan. Nobiletin and tangeretin (citrus polymethoxyflavones): an overview on their chemistry, pharmacology and cytotoxic activities against breast cancer[J]. Journal of Chinese Pharmaceutical Sciences, 2020, 29(7): 443-454.
| [1] Kumar, S.; Pandey, A.K. Chemistry and biological activities of flavonoids: An overview. Sci. World J. 2013, 2013, 1-16.
[2] Singh, M.; Kaur, M.; Silakari, O. Flavones: an important scaffold for medicinal chemistry. Eur. J. Med. Chem. 2014, 84, 206-239.
[3] Lu, Y.H.; Zhang, C.W.; Bucheli, P.; Wei, D.Z. Citrus flavonoids in fruit and traditional Chinese medicinal food ingredients in China. Plant Foods Hum. Nutr. 2006, 61, 57-65.
[4] Li, S.M.; Wang, H.; Guo, L.M.; Zhao, H.; Ho, C.T. Chemistry and bioactivity of nobiletin and its metabolites. J. Funct. Foods. 2014, 6, 2-10.
[5] Li, S.M.; Pan, M.H.; Lo, C.Y.; Tan, D.; Wang, Y.; Shahidi, F.; Ho, C.T. Chemistry and health effects of polymethoxyflavones and hydroxylated polymethoxyflavones. J. Funct. Foods. 2009, 1, 2-12.
[6] Gao, Z.; Gao, W.; Zeng, S.L.; Li, P.; Liu, E.H. Chemical structures, bioactivities and molecular mechanisms of Citrus polymethoxyflavones. J. Funct. Foods. 2018, 40, 498-509.
[7] Nogata, Y.; Sakamoto, K.; Shiratsuchi, H.; Ishii, T.; Yano, M.; Ohta, H. Flavonoid composition of fruit tissues of Citrus species. Biosci. Biotechnol. Biochem. 2006, 70, 178-192.
[8] Du, Q.Z.; Chen, H. The methoxyflavones in Citrus reticulata Blanco cv. ponkan and their antiproliferative activity against cancer cells. Food Chem. 2010, 119, 567-572.
[9] Abe, S.; Fan, K.H.; Ho, C.T.; Ghai, G.; Yang, K. Chemopreventive effects of orange peel extract (OPE). II: OPE inhibits atypical hyperplastic lesions in rodent mammary gland. J. Med. Food. 2007, 10, 18-24.
[10] Cao, G.; Fu, Q.; Zhang, C.; Wang, H.; Chen, S.Z. Rapid characterization of 96 chemical constituents in Citri Reticulatae Folium (leaves of „Fuju‟) using HPLC-DAD-ESI-MSn. J. Chin. Pharm. Sci. 2016, 25, 91-110.
[11] Yu, X.; Sun, S.; Guo, Y.Y.; Liu, Y.; Yang, D.Y.; Li, G.Y.; Lü, S. Citri Reticulatae Pericarpium (Chenpi): Botany, ethnopharmacology, phytochemistry, and pharmacology of a frequently used traditional Chinese medicine. J. Ethnopharmacol. 2018, 220, 265-282.
[12] Li, S.M.; Pan, M.H.; Lo, C.Y.; Tan, D.; Wang, Y.; Shahidi, F.; Ho, C.T. Chemistry and health effects of polymethoxyflavones and hydroxylated polymethoxyflavones. J. Funct. Foods. 2009, 1, 2-12.
[13] Rawson, N.E.; Ho, C.T.; Li, S.M. Efficacious anti-cancer property of flavonoids from Citrus peels. Food Sci. Hum. Wellness. 2014, 3, 104-109.
[14] Wang, L.W.; Wang, J.H.; Fang, L.Y.; Zheng, Z.L.; Zhi, D.X.; Wang, S.Y.; Li, S.M.; Ho, C.T.; Zhao, H. Anticancer activities of Citrus peel polymethoxyflavones related to angiogenesis and others. Biomed. Res. Int. 2014, 2014, 453972.
[15] Walle, T.; Ta, N.; Kawamori, T.; Wen, X.; Tsuji, P.A.; Walle, U.K. Cancer chemopreventive properties of orally bioavailable flavonoids: methylated versus unmethylated flavones. Biochem. Pharmacol. 2007, 73, 1288-1296.
[16] Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018, 68, 394-424.
[17] Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2018. CA A Cancer J. Clin. 2018, 68, 7-30.
[18] Carey, L.A. Directed therapy of subtypes of triple-negative breast cancer. Oncologist. 2011, 16 Suppl 1, 71-78.
[19] Huang, H.; Li, L.F.; Shi, W.M.; Liu, H.; Yang, J.Q.; Yuan, X.L.; Wu, L.H. The multifunctional effects of nobiletin and its Metabolites In vivo and In vitro. Ev.id. Based Complement. Alternat. Med. 2016, 2016, 1-14.
[20] Braidy, N.; Behzad, S.; Habtemariam, S.; Ahmed, T.; Daglia, M.; Nabavi, S.M.; Sobarzo-Sanchez, E.; Nabavi, S.F. Neuroprotective effects of Citrus fruit-derived flavonoids, nobiletin and tangeretin in Alzheimer‟s and Parkinson's disease. CNS Neurol. Disord. Drug Targets. 2017, 16, 387-397.
[21] Doogue, M.P.; Polasek, T.M. The ABCD of clinical pharmacokinetics. Ther. Adv. Drug Saf. 2013, 4, 5-7.
[22] Goh, J.X.H.; Tan, L.T.; Goh, J.K.; Chan, K.G.; Pusparajah, P.; Lee, L.H.; Goh, B.H. Nobiletin and derivatives: functional compounds from Citrus fruit peel for colon cancer chemoprevention. Cancers (Basel). 2019, 11, E867.
[23] Wen, X.; Walle, T. Methylated flavonoids have greatly improved intestinal absorption and metabolic stability. Drug Metab. Dispos. 2006, 34, 1786-1792.
[24] Kemperman, R.A.; Bolca, S.; Roger, L.C.; Vaughan, E.E. Novel approaches for analysing gut microbes and dietary polyphenols: challenges and opportunities. Microbiology. 2010, 156, 3224-3231.
[25] Singh, S.P.; Wahajuddin,, Tewari, D.; Patel, K.; Jain, G.K. Permeability determination and pharmacokinetic study of nobiletin in rat plasma and brain by validated high-performance liquid chromatography method. Fitoterapia. 2011, 82, 1206-1214.
[26] Kumar, A.; Devaraj, V.C.; Giri, K.C.; Giri, S.; Rajagopal, S.; Mullangi, R. Development and validation of a highly sensitive LC-MS/MS-ESI method for the determination of nobiletin in rat plasma: application to a pharmacokinetic study. Biomed. Chromatogr. 2012, 26, 1464-1471.
[27] Murakami, A.; Koshimizu, K.; Ohigashi, H.; Kuwahara, S.; Kuki, W.; Takahashi, Y.; Hosotani, K.; Kawahara, S.; Matsuoka, Y. Characteristic rat tissue accumulation of nobiletin, a chemopreventive polymethoxyflavonoid, in comparison with luteolin. Biofactors. 2002, 16, 73-82.
[28] Evans, M.; Sharma, P.; Guthrie, N. Bioavailability of Citrus polymethoxylated flavones and their biological role in metabolic syndrome and hyperlipidemia. Readings in Advanced Pharmacokinetics - Theory, Methods and Applications. InTech. 2012, 267-284.
[29] Hung, W.L.; Chang, W.S.; Lu, W.C.; Wei, G.J.; Wang, Y.; Ho, C.T.; Hwang, L.S. Pharmacokinetics, bioavailability, tissue distribution and excretion of tangeretin in rat. J. Food Drug Anal. 2018, 26, 849-857.
[30] Meiyanto, E.; Hermawan, A.; Junedi, S.; Fitriasari, A.; Susidarti, R.A. Nobiletin increased cytotoxic activity of doxorubicin on MCF-7 cells but not on T47D cells. Int. J. Phytomed. 2011, 3, 129-137.
[31] Surichan, S.; Androutsopoulos, V.P.; Sifakis, S.; Koutala, E.; Tsatsakis, A.; Arroo, R.R.; Boarder, M.R. Bioactivation of the Citrus flavonoid nobiletin by CYP1 enzymes in MCF7 breast adenocarcinoma cells. Food Chem. Toxicol. 2012, 50, 3320-3328.
[32] Takeshima, M.; Ono, M.; Higuchi, T.; Chen, C.; Hara, T.; Nakano, S. Anti-proliferative and apoptosis-inducing activity of lycopene against three subtypes of human breast cancer cell lines. Cancer Sci. 2014, 105, 252-257.
[33] Surichan, S.; Arroo, R.R.; Ruparelia, K.; Tsatsakis, A.M.; Androutsopoulos, V.P. Nobiletin bioactivation in MDA-MB-468 breast cancer cells by cytochrome P450 CYP1 enzymes. Food Chem. Toxicol. 2018, 113, 228-235.
[34] Surichan, S.; Arroo, R.R.; Tsatsakis, A.M.; Androut-sopoulos, V.P. Tangeretin inhibits the proliferation of human breast cancer cells via CYP1A1/CYP1B1 enzyme induction and CYP1A1/CYP1B1-mediated metabolism to the product 4' hydroxy tangeretin. Toxicol. In Vitro. 2018, 50, 274-284.
[35] Fan, S.J.; Xu, H.F.; Liu, H.G.; Hu, Z.C.; Xiao, J.Y.; Liu, H. Inhibition of cancer cell growth by Tangeretin flavone in drug-resistant MDA-MB-231 human breast carcinoma cells is facilitated via targeting cell apoptosis, cell cycle phase distribution, cell invasion and activation of numerous caspases. J. BUON. 2019, 24, 1532-1537.
[36] Morley, K.L.; Ferguson, P.J.; Koropatnick, J. Tangeretin and nobiletin induce G1 cell cycle arrest but not apoptosis in human breast and colon cancer cells. Cancer Lett. 2007, 251, 168-178.
[37] Baek, S.H.; Kim, S.M.; Nam, D.; Lee, J.H.; Ahn, K.S.; Choi, S.H.; Kim, S.H.; Shim, B.S.; Chang, I.M.; Ahn, K.S. Antimetastatic effect of nobiletin through the down-regulation of CXC chemokine receptor type 4 and matrix metallopeptidase-9. Pharm. Biol. 2012, 50, 1210-1218.
[38] Sp, N.; Kang, D.; Joung, Y.; Park, J.; Kim, W.; Lee, H.; Song, K.D.; Park, Y.M.; Yang, Y. Nobiletin inhibits angiogenesis by regulating src/FAK/STAT3-mediated signaling through PXN in ER+ breast cancer cells. Int. J. Mol. Sci. 2017, 18, 935.
[39] Sp, N.; Kang, D.Y.; Kim, D.H.; Park, J.H.; Lee, H.G.; Kim, H.J.; Darvin, P.; Park, Y.M.; Yang, Y.M. Nobiletin inhibits CD36-dependent tumor angiogenesis, migration, invasion, and sphere formation through the Cd36/Stat3/nf-κb signaling Axis. Nutrients. 2018, 10, E772.
[40] Liu, J.L.; Wang, S.; Tian, S.Q.; He, Y.; Lou, H.; Yang, Z.J.; Kong, Y.C.; Cao, X.Y. Nobiletin inhibits breast cancer via p38 mitogen-activated protein kinase, nuclear transcription factor-κB, and nuclear factor erythroid 2-related factor 2 pathways in MCF-7 cells. Food Nutr. Res. 2018, 62, DOI:10.29219/fnr.v62.1323.
[41] Kerdelhué, B.; Forest, C.; Coumoul, X. Dimethyl-benz(a)anthracene: a mammary carcinogen and a neuroendocrine disruptor. Biochim. Open. 2016, 3, 49-55.
[42] van Slambrouck, S.; Parmar, V.S.; Sharma, S.K.; De Bondt, B.; Foré, F.; Coopman, P.; Vanhoecke, B.W.; Boterberg, T.; Depypere, H.T.; Leclercq, G.; Bracke, M.E. Tangeretin inhibits extracellular-signal-regulated kinase (ERK) phosphorylation. FEBS Lett. 2005, 579, 1665-1669.
[43] Meiyanto, E.; Fitriasari, A.; Hermawan, A.; Junedi, S.; Susidarti, R.A. The improvement of doxorubicin activity on breast cancer cell lines by tangeretin through cell cycle modulation. Orient. Pharm. Exp. Med. 2011, 11, 183-190.
[44] Lakshmi, A.; Subramanian, S.P. Tangeretin ameliorates oxidative stress in the renal tissues of rats with experimental breast cancer induced by 7, 12-dimethylbenz[a]anthracene. Toxicol. Lett. 2014, 229, 333-348.
[45] Lakshmi, A.; Subramanian, S. Chemotherapeutic effect of tangeretin, a polymethoxylated flavone studied in 7, 12-dimethylbenz(a)anthracene induced mammary carcinoma in experimental rats. Biochimie. 2014, 99, 96-109.
[46] Arivazhagan, L.; Sorimuthu Pillai, S. Tangeretin, a Citrus pentamethoxy flavone, exerts cytostatic effect via p53/p21 up-regulation and suppresses metastasis in 7, 12-dimethylbenz(a)anthracene-induced rat mammary carcinoma. J. Nutr. Biochem. 2014, 25, 1140-1153.
[47] Arivazhagan, L.; Subramanian, S.P. Tangeretin, a Citrus flavonoid attenuates oxidative stress and protects hepatocellular architecture in rats with 7, 12-dimethylbenz(a)anthracene induced experimental mammary carcinoma. J. Funct. Foods. 2015, 15, 339-353.
[48] Periyasamy, K.; Baskaran, K.; Ilakkia, A.; Vanitha, K.; Selvaraj, S.; Sakthisekaran, D. Antitumor efficacy of tangeretin by targeting the oxidative stress mediated on 7, 12-dimethylbenz(a) anthracene-induced proliferative breast cancer in Sprague-Dawley rats. Cancer Chemother. Pharmacol. 2015, 75, 263-272.
[49] Periyasamy, K.; Sivabalan, V.; Baskaran, K.; Kasthuri, K.; Sakthisekaran, D. Cellular metabolic energy modulation by tangeretin in 7, 12-dimethylbenz(a) anthracene-induced breast cancer. J. Biomed. Res. 2016, 30, 134-141.
[50] Yoshimizu, N.; Otani, Y.; Saikawa, Y.; Kubota, T.; Yoshida, M.; Furukawa, T.; Kumai, K.; Kameyama, K.; Fujii, M.; Yano, M.; Sato, T.; Ito, A.; Kitajima, M. Anti-tumour effects of nobiletin, a Citrus flavonoid, on gastric cancer include: antiproliferative effects, induction of apoptosis and cell cycle deregulation. Aliment. Pharmacol. Ther. 2004, 20, 95-101.
[51] Moon, J.Y.; Cho, S.K. Nobiletin induces protective autophagy accompanied by ER-stress mediated apoptosis in human gastric cancer SNU-16 cells. Molecules. 2016, 21, E914.
[52] Chen, P.Y.; Chen, Y.T.; Gao, W.Y.; Wu, M.J.; Yen, J.H. Nobiletin down-regulates c-KIT gene expression and exerts antileukemic effects on human acute myeloid leukemia cells. J. Agric. Food Chem. 2018, 66, 13423-13434.
[53] Luo, G.; Guan, X.L.; Zhou, L.M. Apoptotic effect of Citrus fruit extract nobiletin on lung cancer cell line A549 in vitro and in vivo. Cancer Biol. Ther. 2008, 7, 966-973.
[54] Zheng, G.D.; Hu, P.J.; Chao, Y.X.; Zhou, Y.; Yang, X.J.; Chen, B.Z.; Yu, X.Y.; Cai, Y. Nobiletin induces growth inhibition and apoptosis in human nasopharyngeal carcinoma C666-1 cells through regulating PARP-2/SIRT1/AMPK signaling pathway. Food Sci. Nutr. 2019, 7, 1104-1112.
[55] Cheng, H.L.; Hsieh, M.J.; Yang, J.S.; Lin, C.W.; Lue, K.H.; Lu, K.H.; Yang, S.F. Nobiletin inhibits human osteosarcoma cells metastasis by blocking ERK and JNK-mediated MMPs expression. Oncotarget. 2016, 7, 35208-35223.
[56] Chen, J.C.; Chen, A.Y.; Huang, H.Z.; Ye, X.Q.; Rollyson, W.D.; Perry, H.E.; Brown, K.C.; Rojanasakul, Y.; Rankin, G.O.; Dasgupta, P.; Chen, Y.C. The flavonoid nobiletin inhibits tumor growth and angiogenesis of ovarian cancers via the Akt pathway. Int. J. Oncol. 2015, 46, 2629-2638.
[57] Guney Eskiler, G.; Deveci, A.O.; Bilir, C.; Kaleli, S. Synergistic effects of nobiletin and sorafenib combination on metastatic prostate cancer cells. Nutr. Cancer. 2019, 71, 1299-1312.
[58] Sousa, D.P.; Pojo, M.; Pinto, A.T.; Leite, V.; Serra, A.T.; Cavaco, B.M. Nobiletin alone or in combination with cisplatin decreases the viability of anaplastic thyroid cancer cell lines. Nutr. Cancer. 2020, 72, 352-363.
[59] Ting, Y.W.; Chiou, Y.S.; Pan, M.H.; Ho, C.T.; Huang, Q.R. In vitro and in vivo anti-cancer activity of tangeretin against colorectal cancer was enhanced by emulsion-based delivery system. J. Funct. Foods. 2015, 15, 264-273.
[60] Dong, Y.; Cao, A.L.; Shi, J.R.; Yin, P.H.; Wang, L.; Ji, G.; Xie, J.Q.; Wu, D.Z. Tangeretin, a Citrus polymethoxy flavonoid, induces apoptosis of human gastric cancer AGS cells through extrinsic and intrinsic signaling pathways. Oncol. Rep. 2014, 31, 1788-1794.
[61] Zhang, X.K.; Zheng, L.M.; Sun, Y.G.; Wang, T.X.; Wang, B.C. Tangeretin enhances radiosensitivity and inhibits the radiation-induced epithelial-mesenchymal transition of gastric cancer cells. Oncol. Rep. 2015, 34, 302-310.
[62] Yumnam, S.; Raha, S.; Kim, S.; Venkatarame Gowda Saralamma, V.; Lee, H.; Ha, S.; Heo, J.; Lee, S.; Kim, E.; Lee, W.; Kim, J.; Kim, G. Identification of a novel biomarker in tangeretin-induced cell death in AGS human gastric cancer cells. Oncol. Rep. 2018, 40, 3249−3260.
[63] Ma, L.L.; Wang, D.W.; Yu, X.D.; Zhou, Y.L. Tangeretin induces cell cycle arrest and apoptosis through upregulation of PTEN expression in glioma cells. Biomed. Pharmacother. 2016, 81, 491-496.
[64] Hirano, T.; Abe, K.; Gotoh, M.; Oka, K. Citrus flavone tangeretin inhibits leukaemic HL-60 cell growth partially through induction of apoptosis with less cytotoxicity on normal lymphocytes. Br. J. Cancer 1995, 72, 1380-1388.
[65] Zheng, J.; Shao, Y.Q.; Jiang, Y.; Chen, F.; Liu, S.L.; Yu, N.H.; Zhang, D.D.; Liu, X.H.; Zou, L.H. Tangeretin inhibits hepatocellular carcinoma proliferation and migration by promoting autophagy-related BECLIN1. Cancer Manag. Res. 2019, 11, 5231-5242.
[66] Chen, K.H.; Weng, M.S.; Lin, J.K. Tangeretin suppresses IL-1beta-induced cyclooxygenase (COX)-2 expression through inhibition of p38 MAPK, JNK, and AKT activation in human lung carcinoma cells. Biochem. Pharmacol. 2007, 73, 215-227.
[67] Li, Y.R.; Li, S.M.; Ho, C.T.; Chang, Y.H.; Tan, K.T.; Chung, T.W.; Wang, B.Y.; Chen, Y.K.; Lin, C.C. Tangeretin derivative, 5-acetyloxy-6, 7, 8, 4'-tetramethoxyflavone induces G2/M arrest, apoptosis and autophagy in human non-small cell lung cancer cells in vitro and in vivo. Cancer Biol. Ther. 2016, 17, 48-64.
[68] Arafa, E.S.A.; Zhu, Q.Z.; Barakat, B.M.; Wani, G.; Zhao, Q.; El-Mahdy, M.A.; Wani, A.A. Tangeretin sensitizes cisplatin-resistant human ovarian cancer cells through downregulation of phosphoinositide 3-kinase/Akt signaling pathway. Cancer Res. 2009, 69, 8910-8917.
[69] Zhu, W.B.; Xiao, N.; Liu, X.J. Dietary flavonoid tangeretin induces reprogramming of epithelial to mesenchymal transition in prostate cancer cells by targeting the PI3K/Akt/mTOR signaling pathway. Oncol. Lett. 2018, 15, 433-440.
[70] Kawaii, S.; Tomono, Y.; Katase, E.; Ogawa, K.; Yano, M. Quantitation of flavonoid constituents in Citrus fruits. J. Agric. Food Chem. 1999, 47, 3565-3571.
[71] Manthey, J.A.; Guthrie, N. Antiproliferative activities of Citrus flavonoids against six human cancer cell lines. J. Agric. Food Chem. 2002, 50, 5837-5843.
[72] Li, S.M.; Pan, M.H.; Lai, C.S.; Lo, C.Y.; Dushenkov, S.; Ho, C.T. Isolation and syntheses of polymethoxyflavones and hydroxylated polymethoxyflavones as inhibitors of HL-60 cell lines. Bioorg. Med. Chem. 2007, 15, 3381-3389.
[73] Qiu, P.J.; Dong, P.; Guan, H.S.; Li, S.M.; Ho, C.T.; Pan, M.H.; McClements, D.J.; Xiao, H. Inhibitory effects of 5-hydroxy polymethoxyflavones on colon cancer cells. Mol. Nutr. Food Res. 2010, 54 Suppl 2, S244-S252.
[74] Charoensinphon, N.; Qiu, P.J.; Dong, P.; Zheng, J.K.; Ngauv, P.; Cao, Y.; Li, S.M.; Ho, C.T.; Xiao, H. 5-Demethyltangeretin inhibits human nonsmall cell lung cancer cell growth by inducing G2/M cell cycle arrest and apoptosis. Mol. Nutr. Food Res. 2013, 57, 2103-2111.
[75] Manthey, J.A.; Cesar, T.B.; Jackson, E.; Mertens-Talcott, S. Pharmacokinetic study of nobiletin and tangeretin in rat serum by high-performance liquid chromatography-electrospray ionization-mass spectrometry. J. Agric. Food Chem. 2011, 59, 145-151. |
| [1] | Xiaohui Du, Hongyan Yang, Tao Wang, Hongxia Cui, Yu Lin, Hongling Li. Deciphering the latent mechanism of nobiletin in the treatment of metabolic syndrome based on network pharmacology and molecular docking [J]. Journal of Chinese Pharmaceutical Sciences, 2022, 31(11): 803-823. |
| [2] | Ling Zhang, Wei Chen, Ningning Yao, Shuzeng Hou, Zhiwei Meng, Yi Kong, Chenzhong Liao, Zhouling Xie. Discovery of novel aspartate derivatives as highly potent and selective FXIa inhibitors [J]. Journal of Chinese Pharmaceutical Sciences, 2022, 31(10): 727-737. |
| [3] | Xin Dong, Hong Wang, Feixiang Ma, Jianping Gao, Shizhong Chen, Peifeng Xue. A strategy for structure-activity relationship study on antioxidants in Echinops latifolius Tausch extracts by online HPLC-radical scavenging detection coupled with ESI-IT-TOF-MSn [J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(4): 267-279. |
| [4] | Eric Wei Chiang Chan, Siu Kuin Wong, Joseph Tangah, Tomomi Inoue, Hung Tuck Chan. A synopsis on flavonoids from the roots of Scutellaria baicalensis with some insights on baicalein and its anti-cancer properties [J]. Journal of Chinese Pharmaceutical Sciences, 2019, 28(4): 217-228. |
| [5] | Zongze Huang, Xintong Wang, Ying Meng, Xin Li, Haoran Xiao, Xiling Bian, KeWei Wang, Qi Sun. The design, synthesis and α7 nicotinic acetylcholine receptors positive allosteric modulative evaluation of 3H-quinazolin-4-one derivatives [J]. Journal of Chinese Pharmaceutical Sciences, 2018, 27(8): 540-552. |
| [6] | Jiayuan Jiao, Hao Hu, Siyuan Wei, Wanqiu Wang, He Lin, Baoshan Chai. Design, synthesis and antitumor activity evaluation of novel 2,6-dichloro-3,5-dinitrotoluene derivatives [J]. Journal of Chinese Pharmaceutical Sciences, 2018, 27(3): 159-169. |
| [7] | Guanghua Peng, Wenxi Zhang, Maoyuan Song, Mengya Yin, Jiaxing Wang, Jiajia Li, Yajie Liu, Yuanyuan Zhang, Xinru Li, Guiling Li. The relationship between structural parameters and antibacterial biofilm activity for alkyl rhamnoside as a novel amphiphilic material [J]. Journal of Chinese Pharmaceutical Sciences, 2018, 27(12): 817-823. |
| [8] | Shunan Tang, Wei Huang, Shuai Ji, Yongrui Wang, Daoyong Pei, Min Ye, Siwang Yu. Prenylated flavonoids from Glycyrrhiza uralensis as promising anti-cancer agents: a preliminary structure-activity study [J]. Journal of Chinese Pharmaceutical Sciences, 2016, 25(1): 23-29. |
| [9] | Jianguo Li, Fen Pei, Wenjie Zhu, Hongwei Jin, Yongjuan Zhao, Liangren Zhang, Honcheung Lee, Lihe Zhang. Investigation of the effect of 2'-substitution of NMN analogues on CD38 NADase inhibitory activity [J]. Journal of Chinese Pharmaceutical Sciences, 2015, 24(8): 514-523. |
| [10] | Yuanyuan Jin, Juanjuan Liu, Xiaozhou Feng, Yadong Li, Wan Sun, Kangyou Wang, Xifeng Tian, Zhaoyong Yang. Advances of bacterial transferase MraY and its inhibitors [J]. Journal of Chinese Pharmaceutical Sciences, 2015, 24(3): 137-147. |
| [11] | Liang Guo, Wenxi Fan, Ziyun Gan, Wei Chen, Qin Ma, Rihui Cao. Design and synthesis of 1-substituted-β-carboline derivatives as potential anticancer agents [J]. Journal of Chinese Pharmaceutical Sciences, 2015, 24(12): 801-808. |
| [12] | Yunong Pang, Jun Hu, Yushuang Chai, Hao Wu, Yugang Wang, Fan Lei, Dongming Xing, Lijun Du. Comparison of berberine and its five analogues on cell viability and COX-2 expression during glucose-oxygen deprivation and reperfusion in PC12 cells [J]. Journal of Chinese Pharmaceutical Sciences, 2014, 23(9): 617-625. |
| [13] | Lei Zhang, Xin-Shan Ye*. Structure modifications based on KRN7000 and their SARs in activating NKT cells [J]. , 2008, 17(4): 263-271. |
| [14] |
Xue Zhang, Jie-Kun Xu, Nai-Li Wang, Hiroshi Kurihara, Xin-Sheng Yao* . Antioxidant phenanthrenes and lignans from Dendrobium nobile [J]. , 2008, 17(4): 314-318. |
| [15] | DU Lü-pei, LI Min-yong, XIA Lin*, YOU Qi-dong. A 3D-QSAR Study on a Novel Chromanol Class of IKs Potassium Channel Blockers [J]. , 2005, 14(2): 89-94. |
| Viewed | ||||||
|
Full text |
|
|||||
|
Abstract |
|
|||||
