Generic placeholder image

Recent Patents on Anti-Cancer Drug Discovery

Author(s): Hongyu Tao, Ling Zuo, Huanli Xu, Cong Li, Gan Qiao, Mingyue Guo and Xiukun Lin*

DOI: 10.2174/1574892815666200131120618

DownloadDownload PDF Flyer Cite As
Alkaloids as Anticancer Agents: A Review of Chinese Patents in Recent 5 Years

Page: [2 - 13] Pages: 12

  • * (Excluding Mailing and Handling)

Explore Articles
About Journal
For Authors
For Editors
For Reviewers

Abstract

Background: In recent years, many novel alkaloids with anticancer activity have been found in China, and some of them are promising for developing as anticancer agents.

Objective: This review aims to provide a comprehensive overview of the information about alkaloid anticancer agents disclosed in Chinese patents, and discusses their potential to be developed as anticancer drugs used clinically.

Methods: Anticancer alkaloids disclosed in Chinese patents in recent 5 years were presented according to their mode of actions. Their study results published on PubMed, and SciDirect databases were presented.

Results: More than one hundred anticancer alkaloids were disclosed in Chinese patents and their mode of action referred to arresting cell cycle, inhibiting protein kinases, affecting DNA synthesis and p53 expression, etc.

Conclusion: Many newly found alkaloids displayed potent anticancer activity both in vitro and in vivo, and some of the anticancer alkaloids acted as protein kinase inhibitors or CDK inhibitors possess the potential for developing as novel anticancer agents.

Keywords: Alkaloids, anticancer, cell circle arrest, DNA damage, p53 expression, protein kinase inhibitor.

[1]
Schläger S, Dräger B. Exploiting plant alkaloids. Curr Opin Biotechnol 2016; 37: 155-64.
[http://dx.doi.org/10.1016/j.copbio.2015.12.003] [PMID: 26748036]
[2]
Yang CH, Horwitz SB. Taxol®: The first microtubule stabilizing agent. Int J Mol Sci 2017; 18(8): 1733.
[http://dx.doi.org/10.3390/ijms18081733] [PMID: 28792473]
[3]
Shah NN, Merchant MS, Cole DE, et al. Vincristine Sulfate Liposomes Injection (VSLI, Marqibo(R)): Results from a Phase I study in children, adolescents, and young adults with refractory solid tumors or leukemias. Pediatr Blood Cancer 2016; 63(6): 997-1005.
[http://dx.doi.org/10.1002/pbc.25937] [PMID: 26891067]
[4]
Martino E, Della Volpe S, Terribile E, et al. The long story of camptothecin: From traditional medicine to drugs. Bioorg Med Chem Lett 2017; 27(4): 701-7.
[http://dx.doi.org/10.1016/j.bmcl.2016.12.085] [PMID: 28073672]
[5]
Whittaker SR, Mallinger A, Workman P, Clarke PA. Inhibitors of cyclin-dependent kinases as cancer therapeutics. Pharmacol Ther 2017; 173: 83-105.
[http://dx.doi.org/10.1016/j.pharmthera.2017.02.008] [PMID: 28174091]
[6]
Malumbres M. Cyclin-dependent kinases. Genome Biol 2014; 15(6): 122.
[http://dx.doi.org/10.1186/gb4184] [PMID: 25180339]
[7]
Peeper DS, Upton TM, Ladha MH, et al. Ras signalling linked to the cell-cycle machinery by the retinoblastoma protein. Nature 1997; 386(6621): 177-81.
[http://dx.doi.org/10.1038/386177a0] [PMID: 9062190]
[8]
Narasimha AM, Kaulich M, Shapiro GS, Choi YJ, Sicinski P, Dowdy SF. Cyclin D activates the Rb tumor suppressor by monophosphorylation. Elife 2014; 3.
[http://dx.doi.org/10.7554/eLife.02872] [PMID: 24876129]
[9]
Sísa M, Pla D, Altuna M, et al. Total synthesis and antiproliferative activity screening of (+/-)-aplicyanins A, B and E and related analogues. J Med Chem 2009; 52(20): 6217-23.
[http://dx.doi.org/10.1021/jm900544z] [PMID: 19827832]
[10]
Walker SR, Carter EJ, Huff BC, Morris JC. Variolins and related alkaloids. Chem Rev 2009; 109(7): 3080-98.
[http://dx.doi.org/10.1021/cr900032s] [PMID: 19489543]
[11]
Endo T, Tsuda M, Fromont J, Kobayashi J. Hyrtinadine A, a bis-indole alkaloid from a marine sponge. J Nat Prod 2007; 70(3): 423-4.
[http://dx.doi.org/10.1021/np060420n] [PMID: 17378531]
[12]
Yadav RR, Sharma S, Joshi P, et al. Meridianin derivatives as potent Dyrk1A inhibitors and neuroprotective agents. Bioorg Med Chem Lett 2015; 25(15): 2948-52.
[http://dx.doi.org/10.1016/j.bmcl.2015.05.034] [PMID: 26048785]
[13]
Gompel M, Leost M, De Kier Joffe EB, et al. Meridianins, a new family of protein kinase inhibitors isolated from the ascidian Aplidium meridianum. Bioorg Med Chem Lett 2004; 14(7): 1703-7.
[http://dx.doi.org/10.1016/j.bmcl.2004.01.050] [PMID: 15026054]
[14]
Jiang T, Zhang HL, Yin RJ, Zhong TJ, Liu L, Dong XY. Derivatives of indole - pyrimidine marine alkaloids Meridianin G and their preparation and application. CN108218837. (2018).
[15]
Soni R, Muller L, Furet P, et al. Inhibition of cyclin-dependent kinase 4 (Cdk4) by fascaplysin, a marine natural product. Biochem Biophys Res Commun 2000; 275(3): 877-84.
[http://dx.doi.org/10.1006/bbrc.2000.3349] [PMID: 10973815]
[16]
Hörmann A, Chaudhuri B, Fretz H. DNA binding properties of the marine sponge pigment fascaplysin. Bioorg Med Chem 2001; 9(4): 917-21.
[http://dx.doi.org/10.1016/S0968-0896(00)00313-8] [PMID: 11354674]
[17]
He D, Sun XF, Yang ZQ, Hou M. β-Carboline alkaloids and their applications in the preparation of antitumor drugs. CN105753860. (2016).
[18]
Meng F, Cai X, Duan J, Matteucci MG, Hart CP. A novel class of tubulin inhibitors that exhibit potent antiproliferation and in vitro vessel-disrupting activity. Cancer Chemother Pharmacol 2008; 61(6): 953-63.
[http://dx.doi.org/10.1007/s00280-007-0549-x] [PMID: 17639393]
[19]
Dumontet C, Jordan MA. Microtubule-binding agents: a dynamic field of cancer therapeutics. Nat Rev Drug Discov 2010; 9(10): 790-803.
[http://dx.doi.org/10.1038/nrd3253] [PMID: 20885410]
[20]
Jordan A, Hadfield JA, Lawrence NJ, McGown AT. Tubulin as a Target for Anticancer Drugs Agents which Interact with the Mitotic Spindle. John Wiley & Sons, Inc. 1998; pp. 259-96.
[21]
Prota AE, Bargsten K, Zurwerra D, et al. Molecular mechanism of action of microtubule-stabilizing anticancer agents. Science 2013; 339(6119): 587-90.
[http://dx.doi.org/10.1126/science.1230582] [PMID: 23287720]
[22]
Bernabeu E, Cagel M, Lagomarsino E, Moretton M, Chiappetta DA. Paclitaxel: What has been done and the challenges remain ahead. Int J Pharm 2017; 526(1-2): 474-95.
[http://dx.doi.org/10.1016/j.ijpharm.2017.05.016] [PMID: 28501439]
[23]
Orr GA, Verdier-Pinard P, McDaid H, Horwitz SB. Mechanisms of Taxol resistance related to microtubules. Oncogene 2003; 22(47): 7280-95.
[http://dx.doi.org/10.1038/sj.onc.1206934] [PMID: 14576838]
[24]
Li Y, Chen Z, Cui Y, Zhai G, Li L. The construction and characterization of hybrid paclitaxel-in-micelle-in-liposome systems for enhanced oral drug delivery. Colloids Surf B Biointerfaces 2017; 160: 572-80.
[http://dx.doi.org/10.1016/j.colsurfb.2017.10.016] [PMID: 29028605]
[25]
Jeon H, Kim J, Lee YM, et al. Poly-paclitaxel/cyclodextrin-SPION nano-assembly for magnetically guided drug delivery system. J Control Release 2016; 231: 68-76.
[http://dx.doi.org/10.1016/j.jconrel.2016.01.006] [PMID: 26780174]
[26]
Tian R, Wang H, Niu R, Ding D. Drug delivery with nanospherical supramolecular cell penetrating peptide-taxol conjugates containing a high drug loading. J Colloid Interface Sci 2015; 453: 15-20.
[http://dx.doi.org/10.1016/j.jcis.2015.04.028] [PMID: 25956129]
[27]
Marupudi NI, Han JE, Li KW, Renard VM, Tyler BM, Brem H. Paclitaxel: a review of adverse toxicities and novel delivery strategies. Expert Opin Drug Saf 2007; 6(5): 609-21.
[http://dx.doi.org/10.1517/14740338.6.5.609] [PMID: 17877447]
[28]
Kundranda MN, Niu J. Albumin-bound paclitaxel in solid tumors: clinical development and future directions. Drug Des Devel Ther 2015; 9: 3767-77.
[http://dx.doi.org/10.2147/DDDT.S88023] [PMID: 26244011]
[29]
Yu JQ, Wei YL, Xie ZF, Lei JC. Application of amide alkaloids in the preparation of chemotherapeutic sensitizers and antitumor drug compositions. CN109875998. (2019).
[30]
Ren J, Xu Y, Huang Q, et al. Chabamide induces cell cycle arrest and apoptosis by the Akt/MAPK pathway and inhibition of P-glycoprotein in K562/ADR cells. Anticancer Drugs 2015; 26(5): 498-507.
[http://dx.doi.org/10.1097/CAD.0000000000000209] [PMID: 25714087]
[31]
Cai LL. An anticancer drug composition and its preparation and a preparation method thereof. CN106581012. (2017).
[32]
Zhao YF, Guo RT, Zhang YY, Pang Y. An anticancer drug composition containing taxol. CN106727535. (2017).
[33]
Zhang YH. Water soluble taxol anticancer drug compound and its preparation method and application. CN106554329. (2017).
[34]
Saraswati S, Kanaujia PK, Kumar S, Kumar R, Alhaider AA. Tylophorine, a phenanthraindolizidine alkaloid isolated from Tylophora indica exerts antiangiogenic and antitumor activity by targeting vascular endothelial growth factor receptor 2-mediated angiogenesis. Mol Cancer 2013; 12: 82.
[http://dx.doi.org/10.1186/1476-4598-12-82] [PMID: 23895055]
[35]
Min HY, Chung HJ, Kim EH, Kim S, Park EJ, Lee SK. Inhibition of cell growth and potentiation of tumor necrosis factor-α (TNF-α)-induced apoptosis by a phenanthroindolizidine alkaloid antofine in human colon cancer cells. Biochem Pharmacol 2010; 80(9): 1356-64.
[http://dx.doi.org/10.1016/j.bcp.2010.07.026] [PMID: 20674553]
[36]
Jin HR, Jin SZ, Cai XF, et al. Cryptopleurine targets NF-κB pathway, leading to inhibition of gene products associated with cell survival, proliferation, invasion, and angiogenesis. PLoS One 2012; 7(6) e40355
[http://dx.doi.org/10.1371/journal.pone.0040355] [PMID: 22768286]
[37]
Chemler SR. Phenanthroindolizidines and phenanthroquinolizidines: Promising alkaloids for anti-cancer therapy. Curr Bioact Compd 2009; 5(1): 2-19.
[http://dx.doi.org/10.2174/157340709787580928] [PMID: 20160962]
[38]
Rao KN, Venkatachalam SR. Inhibition of dihydrofolate reductase and cell growth activity by the phenanthroindolizidine alkaloids pergularinine and tylophoridine the in vitro cytotoxicity of these plant alkaloids. Toxicol In Vitro 2000; 14: 53-9.
[http://dx.doi.org/10.1016/S0887-2333(99)00092-2] [PMID: 10699361]
[39]
Lee KH, Yang XM, Shi Q, et al. Antofine and cryptopleurine derivatives as anticancer agents. US9216977. (2015).
[40]
Yang X, Shi Q, Bastow KF, Lee KH. Antitumor agents. 274. A new synthetic strategy for E-ring SAR study of antofine and cryptopleurine analogues. Org Lett 2010; 12(7): 1416-9.
[http://dx.doi.org/10.1021/ol902819j] [PMID: 20196574]
[41]
Yang X, Shi Q, Yang SC, et al. Antitumor agents 288: design, synthesis, SAR, and biological studies of novel heteroatom-incorporated antofine and cryptopleurine analogues as potent and selective antitumor agents. J Med Chem 2011; 54(14): 5097-107.
[http://dx.doi.org/10.1021/jm200330s] [PMID: 21668000]
[42]
Yang X, Shi Q, Lai CY, et al. Antitumor agents 295. E-ring hydroxylated antofine and cryptopleurine analogues as antiproliferative agents: design, synthesis, and mechanistic studies. J Med Chem 2012; 55(15): 6751-61.
[http://dx.doi.org/10.1021/jm3001218] [PMID: 22823514]
[43]
Yang X, Shi Q, Liu YN, et al. Antitumor agents 268. Design, synthesis, and mechanistic studies of new 9-substituted phenanthrene-based tylophorine analogues as potent cytotoxic agents. J Med Chem 2009; 52(16): 5262-8.
[http://dx.doi.org/10.1021/jm9009263] [PMID: 19645447]
[44]
Parrales A, Iwakuma T. Targeting oncogenic mutant p53 for cancer therapy. Front Oncol 2015; 5: 288.
[http://dx.doi.org/10.3389/fonc.2015.00288] [PMID: 26732534]
[45]
Derevyanchuk M, Kretynin S, Iakovenko O, et al. Effect of 24-epibrassinolide on Brassica napus alternative respiratory pathway, guard cells movements and phospholipid signaling under salt stress. Steroids 2017; 117: 16-24.
[http://dx.doi.org/10.1016/j.steroids.2016.11.006] [PMID: 27913097]
[46]
Chu B, Chen C, Li J, et al. Effects of Tibetan turnip (Brassica rapa L.) on promoting hypoxia-tolerance in healthy humans. J Ethnopharmacol 2017; 195: 246-54.
[http://dx.doi.org/10.1016/j.jep.2016.11.028] [PMID: 27856303]
[47]
Zhuang AH. A novel indole alkaloid compound, its preparation method and medicinal application. CN106083863. (2016).
[48]
Wang L, Zhang Y, Wang Z, et al. The antinociceptive properties of the Corydalis yanhusuo extract. PLoS One 2016; 11(9) e0162875
[http://dx.doi.org/10.1371/journal.pone.0162875] [PMID: 27622550]
[49]
Li TJ, Wang S, Meng XS, Bao YR, Guan SS, Liu B. Metabolomics coupled with multivariate data and pathway analysis on potential biomarkers in gastric ulcer and intervention effects of Corydalis yanhusuo alkaloid. PLoS One 2014; 9(1) e82499
[http://dx.doi.org/10.1371/journal.pone.0082499] [PMID: 24454691]
[50]
Ling H, Wu L, Li L. Corydalis yanhusuo rhizoma extract reduces infarct size and improves heart function during myocardial ischemia/reperfusion by inhibiting apoptosis in rats. Phytother Res 2006; 20(6): 448-53.
[http://dx.doi.org/10.1002/ptr.1875] [PMID: 16619356]
[51]
Xu Z. A novel indole alkaloid compound, its preparation method and medicinal application. CN105906645. (2016).
[52]
Le VH, Inai M, Williams RM, Kan T. Ecteinascidins. A review of the chemistry, biology and clinical utility of potent tetrahydroisoquinoline antitumor antibiotics. Nat Prod Rep 2015; 32(2): 328-47.
[http://dx.doi.org/10.1039/C4NP00051J] [PMID: 25273374]
[53]
Leal JF, Martínez-Díez M, García-Hernández V, et al. PM01183, a new DNA minor groove covalent binder with potent in vitro and in vivo anti-tumour activity. Br J Pharmacol 2010; 161(5): 1099-110.
[http://dx.doi.org/10.1111/j.1476-5381.2010.00945.x] [PMID: 20977459]
[54]
Ocania VM, Nunez HS. Antitumor alkaloid combination therapy. CN105664165. (2016).
[55]
Albert M, Helin K. Histone methyltransferases in cancer. Semin Cell Dev Biol 2010; 21(2): 209-20.
[http://dx.doi.org/10.1016/j.semcdb.2009.10.007] [PMID: 19892027]
[56]
Cao H, Li L, Yang D, et al. Recent progress in histone methyltransferase (G9a) inhibitors as anticancer agents. Eur J Med Chem 2019; 179: 537-46.
[http://dx.doi.org/10.1016/j.ejmech.2019.06.072] [PMID: 31276898]
[57]
Gehling VS, Vaswani RG, Nasveschuk CG, et al. Discovery, design, and synthesis of indole-based EZH2 inhibitors. Bioorg Med Chem Lett 2015; 25(17): 3644-9.
[http://dx.doi.org/10.1016/j.bmcl.2015.06.056] [PMID: 26189078]
[58]
Vaswani RG, Gehling VS, Dakin LA, et al. Identification of (R)-N-((4-Methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)ethyl)-1H-indole-3-carboxamide (CPI-1205), a Potent and Selective Inhibitor of Histone Methyltransferase EZH2, Suitable for Phase I Clinical Trials for B-Cell Lymphomas. J Med Chem 2016; 59(21): 9928-41.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01315] [PMID: 27739677]
[59]
Liu ZQ, Lu LL, Liao GC, et al. A group of anti-tumor indole alkaloids and its preparation method and application. CN109824664. (2019).
[60]
Cui J, Sun W, Hao X, et al. EHMT2 inhibitor BIX-01294 induces apoptosis through PMAIP1-USP9X-MCL1 axis in human bladder cancer cells. Cancer Cell Int 2015; 15(1): 4.
[http://dx.doi.org/10.1186/s12935-014-0149-x] [PMID: 25685062]
[61]
Cao YP, Sun JY, Li MQ, et al. Inhibition of G9a by a small molecule inhibitor, UNC0642, induces apoptosis of human bladder cancer cells. Acta Pharmacol Sin 2019; 40(8): 1076-84.
[http://dx.doi.org/10.1038/s41401-018-0205-5] [PMID: 30765842]
[62]
Pommier Y, Sun Y, Huang SN, Nitiss JL. Roles of eukaryotic topoisomerases in transcription, replication and genomic stability. Nat Rev Mol Cell Biol 2016; 17(11): 703-21.
[http://dx.doi.org/10.1038/nrm.2016.111] [PMID: 27649880]
[63]
Bailly C. Contemporary challenges in the design of topoisomerase II inhibitors for cancer chemotherapy. Chem Rev 2012; 112(7): 3611-40.
[http://dx.doi.org/10.1021/cr200325f] [PMID: 22397403]
[64]
Capranico G, Marinello J, Baranello L. Dissecting the transcriptional functions of human DNA topoisomerase I by selective inhibitors: implications for physiological and therapeutic modulation of enzyme activity. Biochim Biophys Acta 2010; 1806(2): 240-50.
[PMID: 20600630]
[65]
Xu Y, Jing D, Chen R, et al. Design, synthesis and evaluation of novel sophoridinic imine derivatives containing conjugated planar structure as potent anticancer agents. Bioorg Med Chem 2018; 26(14): 4136-44.
[http://dx.doi.org/10.1016/j.bmc.2018.07.001] [PMID: 30007563]
[66]
Tao ZW, Li DD, Zhao XM, Dai LL, Shen HS, Liu K. Preparation and application of quinolisidine alkaloid derivatives. CN106496271. (2017).
[67]
Schwartz PA, Murray BW. Protein kinase biochemistry and drug discovery. Bioorg Chem 2011; 39(5-6): 192-210.
[http://dx.doi.org/10.1016/j.bioorg.2011.07.004] [PMID: 21872901]
[68]
Kannaiyan R, Mahadevan D. A comprehensive review of protein kinase inhibitors for cancer therapy. Expert Rev Anticancer Ther 2018; 18(12): 1249-70.
[http://dx.doi.org/10.1080/14737140.2018.1527688] [PMID: 30259761]
[69]
Li LN, Wang L, Cheng YN, Cao ZQ, Zhang XK, Guo XL. Discovery and characterization of 4-hydroxy-2-pyridone derivative sambutoxin as a potent and promising anticancer drug candidate: Activity and molecular mechanism. Mol Pharm 2018; 15(11): 4898-911.
[http://dx.doi.org/10.1021/acs.molpharmaceut.8b00525] [PMID: 30223653]
[70]
Zhang CC, Cao CY, Kubo M, et al. Chemical constituents from Hericium erinaceus promote neuronal survival and potentiate neurite outgrowth via the TrkA/Erk1/2 pathway. Int J Mol Sci 2017; 18(8) E1659
[http://dx.doi.org/10.3390/ijms18081659] [PMID: 28758954]
[71]
Shen T, Morlock G, Zorn H. Production of cyathane type secondary metabolites by submerged cultures of Hericium erinaceus and evaluation of their antibacterial activity by direct bioautography. Fungal Biol Biotechnol 2015; 2: 8.
[http://dx.doi.org/10.1186/s40694-015-0018-y] [PMID: 28955459]
[72]
Guo XL, Li LN, Zhang XK, Cheng YN, Wang L. The application of a 4-hydroxy-2-pyridinone alkaloid in the preparation of anti-tumor products. CN107536833. (2018).
[73]
Tran TD, Cartner LK, Bokesch HR, et al. NMR characterization of rearranged staurosporine aglycone analogues from the marine sponge Damiria sp. Magn Reson Chem 2019.
[http://dx.doi.org/10.1002/mrc.4932] [PMID: 31379005]
[74]
Van Arnam EB, Ruzzini AC, Sit CS, Currie CR, Clardy J. A Rebeccamycin analog provides plasmid-encoded niche defense. J Am Chem Soc 2015; 137(45): 14272-4.
[http://dx.doi.org/10.1021/jacs.5b09794] [PMID: 26535611]
[75]
Roux PP, Dorval G, Boudreau M, et al. K252a and CEP1347 are neuroprotective compounds that inhibit mixed-lineage kinase-3 and induce activation of Akt and ERK. J Biol Chem 2002; 277(51): 49473-80.
[http://dx.doi.org/10.1074/jbc.M203428200] [PMID: 12388555]
[76]
Civenni G, Longoni N, Costales P, et al. EC-70124, a novel glycosylated indolocarbazole multikinase inhibitor, reverts tumorigenic and stem cell properties in prostate cancer by inhibiting STAT3 and NF-kappaB. Mol Cancer Ther 2016; 15(5): 806-18.
[http://dx.doi.org/10.1158/1535-7163.MCT-15-0791] [PMID: 26826115]
[77]
Sancelme M, Fabre S, Prudhomme M. Antimicrobial activities of indolocarbazole and bis-indole protein kinase C inhibitors. J Antibiot (Tokyo) 1994; 47(7): 792-8.
[http://dx.doi.org/10.7164/antibiotics.47.792] [PMID: 8071125]
[78]
Castro A, Lemos C, Falcão A, Fernandes AS, Glass NL, Videira A. Rotenone enhances the antifungal properties of staurosporine. Eukaryot Cell 2010; 9(6): 906-14.
[http://dx.doi.org/10.1128/EC.00003-10] [PMID: 20435699]
[79]
Chiu HT, Chen YL, Chen CY, Jin C, Lee MN, Lin YC. Molecular cloning, sequence analysis and functional characterization of the gene cluster for biosynthesis of K-252a and its analogs. Mol Biosyst 2009; 5(10): 1180-91.
[http://dx.doi.org/10.1039/b905293c] [PMID: 19756308]
[80]
Cheng X, Zhou B, Liu H, Huo C, Ding W. One new indolocarbazole alkaloid from the Streptomyces sp. A22. Nat Prod Res 2018; 32(21): 2583-8.
[http://dx.doi.org/10.1080/14786419.2018.1428595] [PMID: 29355042]
[81]
Wang C, Monger A, Wang L, et al. Precursor-directed generation of indolocarbazoles with topoisomerase II alpha inhibitory activity. Mar Drugs 2018; 16(5): 168.
[http://dx.doi.org/10.3390/md16050168]
[82]
Ma ZJ, Wang JH, Ding WJ. An indolecarbazole alkaloid and a preparation method thereof. CN108084205. (2018).
[83]
Li D, Chen J, Ye J, et al. Anti-inflammatory effect of the six compounds isolated from Nauclea officinalis Pierrc ex Pitard, and molecular mechanism of strictosamide via suppressing the NF-κB and MAPK signaling pathway in LPS-induced RAW 264.7 macrophages. J Ethnopharmacol 2017; 196: 66-74.
[http://dx.doi.org/10.1016/j.jep.2016.12.007] [PMID: 27989509]
[84]
Liu QL, Chen AH, Tang JY, et al. A new indole alkaloid with anti-inflammatory activity from Nauclea officinalis. Nat Prod Res 2017; 31(18): 2107-12.
[http://dx.doi.org/10.1080/14786419.2016.1277351] [PMID: 28067066]
[85]
Sun J, Lou H, Dai S, Xu H, Zhao F, Liu K. Indole alkoloids from Nauclea officinalis with weak antimalarial activity. Phytochemistry 2008; 69(6): 1405-10.
[http://dx.doi.org/10.1016/j.phytochem.2008.01.008] [PMID: 18328515]
[86]
Liu YP, Liu QL, Zhang XL, et al. Bioactive monoterpene indole alkaloids from Nauclea officinalis. Bioorg Chem 2019; 83: 1-5.
[http://dx.doi.org/10.1016/j.bioorg.2018.10.013] [PMID: 30339860]
[87]
Fu YH, Liu YP, Liu QL, et al. A novel indole alkaloid compound and a preparation method thereof. CN108358921. (2018).
[88]
Manley PW, Cowan-Jacob SW, Buchdunger E, et al. Imatinib: a selective tyrosine kinase inhibitor. Eur J Cancer 2002; 38(Suppl. 5): S19-27.
[http://dx.doi.org/10.1016/S0959-8049(02)80599-8] [PMID: 12528769]
[89]
Yin Z, Liu T, Fu JX. Two new monoterpenoid indole alkaloids from the leaves and twigs of Ochrosia borbonica. J Asian Nat Prod Res 2019; 21(3): 257-61.
[http://dx.doi.org/10.1080/10286020.2017.1417267] [PMID: 29261331]
[90]
Svoboda GH, Poore GA, Montfort ML. Alkaloids of Ochrosia maculata Jacq. (Ochrosia borbonica Gmel.). Isolation of the alkaloids and study of the antitumor properties of 9-methoxyellipticine. J Pharm Sci 1968; 57(10): 1720-5.
[http://dx.doi.org/10.1002/jps.2600571019] [PMID: 5245921]
[91]
Fu YH, Liu YP, Chen AH, et al. A preparation method of monoterpene indole alkaloids and its application. CN106831775. (2017).
[92]
Parzych KR, Klionsky DJ. An overview of autophagy: morphology, mechanism, and regulation. Antioxid Redox Signal 2014; 20(3): 460-73.
[http://dx.doi.org/10.1089/ars.2013.5371] [PMID: 23725295]
[93]
Levy JMM, Towers CG, Thorburn A. Targeting autophagy in cancer. Nat Rev Cancer 2017; 17(9): 528-42.
[http://dx.doi.org/10.1038/nrc.2017.53] [PMID: 28751651]
[94]
Liao WZ, Chen JY, Li DX, Sun SX, Li ZY, Mao LZ. The preparation and application of piperidine alkaloids. CN109111442. (2019).
[95]
Law YK, Chan WK, Xu SW, et al. Natural small-molecule enhancers of autophagy induce autophagic cell death in apoptosis-defective cells. Sci Rep 2014; 4(1): 5510.
[http://dx.doi.org/10.1038/srep05510] [PMID: 24981420]
[96]
Law YK, Mok WF, Chan WK, et al. Hernandezine, a novel AMPK activator induces autophagic cell death in drug-resistant cancers. Oncotarget 2016; 7(7): 8090-104.
[http://dx.doi.org/10.18632/oncotarget.6980] [PMID: 26811496]
[97]
Law YK, Martínez FG, Qu YQ, et al. Thalidezine, a novel AMPK activator, eliminates apoptosis-resistant cancer cells through energy-mediated autophagic cell death. Oncotarget 2017; 8(18): 30077-91.
[http://dx.doi.org/10.18632/oncotarget.15616] [PMID: 28404910]
[98]
Wong KW, Law YK, Liu L, Wang JR. Group of alkaloids, the novel autophagic enhancers for treatment of cancer and neurodegenerative conditions thereof. US9561223. (2017).
[99]
Kartal-Yandim M, Adan-Gokbulut A, Baran Y. Molecular mechanisms of drug resistance and its reversal in cancer. Crit Rev Biotechnol 2016; 36(4): 716-26.
[PMID: 25757878]
[100]
Dudjak LA. Cancer metastasis. Semin Oncol Nurs 1992; 8(1): 40-50.
[http://dx.doi.org/10.1016/0749-2081(92)90007-P] [PMID: 1546218]
[101]
Bailly C. Lamellarins, from A to Z: a family of anticancer marine pyrrole alkaloids. Curr Med Chem Anticancer Agents 2004; 4(4): 363-78.
[http://dx.doi.org/10.2174/1568011043352939] [PMID: 15281908]
[102]
Baunbaek D, Trinkler N, Ferandin Y, et al. Anticancer alkaloid lamellarins inhibit protein kinases. Mar Drugs 2008; 6(4): 514-27.
[http://dx.doi.org/10.3390/md20080026] [PMID: 19172192]
[103]
Fukuda T, Nanjo Y, Fujimoto M, et al. Lamellarin-inspired potent topoisomerase I inhibitors with the unprecedented benzo[g][1]benzopyrano[4,3-b]indol-6(13H)-one scaffold. Bioorg Med Chem 2019; 27(2): 265-77.
[http://dx.doi.org/10.1016/j.bmc.2018.11.037] [PMID: 30553626]
[104]
Kamiyama H, Kubo Y, Sato H, et al. Synthesis, structure-activity relationships, and mechanism of action of anti-HIV-1 lamellarin α 20-sulfate analogues. Bioorg Med Chem 2011; 19(24): 7541-50.
[http://dx.doi.org/10.1016/j.bmc.2011.10.030] [PMID: 22071527]
[105]
Krishnaiah P, Reddy VLN, Venkataramana G, et al. New lamellarin alkaloids from the Indian ascidian Didemnum obscurum and their antioxidant properties. J Nat Prod 2004; 67(7): 1168-71.
[http://dx.doi.org/10.1021/np030503t] [PMID: 15270574]
[106]
Vanhuyse M, Kluza J, Tardy C, et al. Lamellarin D: a novel pro-apoptotic agent from marine origin insensitive to P-glycoprotein-mediated drug efflux. Cancer Lett 2005; 221(2): 165-75.
[http://dx.doi.org/10.1016/j.canlet.2004.09.022] [PMID: 15808402]
[107]
Xie ZY, Li F, Xu ZH, et al. Pyrrole [2, 1-a] isoquinoline alkaloid and its preparation method and application. CN107522697. (2017).
[108]
Wang HL, Qin N, Liu J, et al. Synthesis and antimetastatic effects of E-salignone amide derivatives. Drug Dev Res 2014; 75(2): 76-87.
[http://dx.doi.org/10.1002/ddr.21157] [PMID: 24648170]
[109]
Duan HQ, Qin N, Jin MN, Shou XY, Gan CC, Liu Q. A progesterane alkaloid derivative with anti-metastasis effect of breast cancer and its medicinal use. CN104744547. (2015).
[110]
Zhai HY, Zhao C, Zhang N, et al. Alkaloids from Pachysandra terminalis inhibit breast cancer invasion and have potential for development as antimetastasis therapeutic agents. J Nat Prod 2012; 75(7): 1305-11.
[http://dx.doi.org/10.1021/np300207c] [PMID: 22804108]
[111]
Zhao C, Gan CC, Jin MN, Tang SA, Qin N, Duan HQ. Antitumor metastasis pregnane alkaloids from Pachysandra terminalis. J Asian Nat Prod Res 2014; 16(5): 440-6.
[http://dx.doi.org/10.1080/10286020.2014.893511] [PMID: 24625225]
[112]
Li XY, Yu Y, Jia M, et al. Terminamines K-S, Antimetastatic Pregnane Alkaloids from the Whole Herb of Pachysandra terminalis. Molecules 2016; 21(10) E1283
[http://dx.doi.org/10.3390/molecules21101283] [PMID: 27681716]
[113]
Coussens LM, Werb Z. Inflammation and cancer. Nature 2002; 420(6917): 860-7.
[http://dx.doi.org/10.1038/nature01322] [PMID: 12490959]
[114]
Liu W, Yi DD, Guo JL, Xiang ZX, Deng LF, He L. Nuciferine, extracted from Nelumbo nucifera Gaertn, inhibits tumor-promoting effect of nicotine involving Wnt/β-catenin signaling in non-small cell lung cancer. J Ethnopharmacol 2015; 165: 83-93.
[http://dx.doi.org/10.1016/j.jep.2015.02.015] [PMID: 25698245]
[115]
Li S, Li HY. An alkaloid is used to block the transformation of inflammatory carcinoma and prevent tumor. CN104510733. (2015).
[116]
Buckley D, Duke G, Heuer TS, et al. Fatty acid synthase - Modern tumor cell biology insights into a classical oncology target. Pharmacol Ther 2017; 177: 23-31.
[http://dx.doi.org/10.1016/j.pharmthera.2017.02.021] [PMID: 28202364]
[117]
Horiguchi A, Asano T, Asano T, Ito K, Sumitomo M, Hayakawa M. Pharmacological inhibitor of fatty acid synthase suppresses growth and invasiveness of renal cancer cells. J Urol 2008; 180(2): 729-36.
[http://dx.doi.org/10.1016/j.juro.2008.03.186] [PMID: 18555493]
[118]
Ding CX, Ma XF, Wang XY, Zhang QL, Luan GX, Suo YR. New applications of benzylisoquinoline alkaloids. CN105168214. (2015).
[119]
Zhang Q, Ma T, Hu N, et al. One step to separate five alkaloids from Hypecoum leptocarpum by high-speed counter-current chromatography. J Chromatogr Sci 2016; 54(3): 466-71.
[PMID: 26499120]
[120]
Zhang Z, Cheng L, Li J, et al. Inhibition of the Wnt/beta-catenin pathway overcomes resistance to enzalutamide in castration-resistant prostate cancer. Cancer Res 2018; 78(12): 3147-62.
[PMID: 29700003]
[121]
Emons G, Spitzner M, Reineke S, et al. Chemoradiotherapy resistance in colorectal cancer cells is mediated by Wnt/beta-catenin signaling. Mol Cancer Res 2017; 15(11): 1481-90.
[http://dx.doi.org/10.1158/1541-7786.MCR-17-0205] [PMID: 28811361]
[122]
Krishnamurthy N, Kurzrock R. Targeting the Wnt/beta-catenin pathway in cancer: Update on effectors and inhibitors. Cancer Treat Rev 2018; 62: 50-60.
[http://dx.doi.org/10.1016/j.ctrv.2017.11.002] [PMID: 29169144]
[123]
Ronaldo AP, Giovanni BR, Maria CFO. The chemistry of Stemona alkaloids: An update. Nat Prod Rep 2010; 27(12): 1908-37.
[http://dx.doi.org/10.1039/c005018k] [PMID: 21042634]
[124]
Ma KQ, Wu XX, Yang P, Yin CX. The preparation and application of a Stemona alkaloid analogue. CN110016041. (2019).
[125]
Umsumarng S, Pitchakarn P, Yodkeeree P, et al. Modulation of P-glycoprotein by Stemona alkaloids in human multidrug resistance leukemic cells and structural relationships. Phytomedicine 2017; 34: 182-90.
[http://dx.doi.org/10.1016/j.phymed.2017.08.004] [PMID: 28899501]
[126]
Yamaoka T, Kusumoto S, Ando K, Ohba M, Ohmori T. Receptor tyrosine kinase-targeted cancer therapy. Int J Mol Sci 2018; 19(11) E3491
[http://dx.doi.org/10.3390/ijms19113491] [PMID: 30404198]
[127]
Carrassa L, Damia G. DNA damage response inhibitors: Mechanisms and potential applications in cancer therapy. Cancer Treat Rev 2017; 60: 139-51.
[http://dx.doi.org/10.1016/j.ctrv.2017.08.013] [PMID: 28961555]
[128]
Zhou L, Wang K, Li Q, Nice EC, Zhang H, Huang C. Clinical proteomics-driven precision medicine for targeted cancer therapy: current overview and future perspectives. Expert Rev Proteomics 2016; 13(4): 367-81.
[http://dx.doi.org/10.1586/14789450.2016.1159959] [PMID: 26923776]
[129]
Zhang J, Wang G, Zhou Y, Chen Y, Ouyang L, Liu B. Mechanisms of autophagy and relevant small-molecule compounds for targeted cancer therapy. Cell Mol Life Sci 2018; 75(10): 1803-26.
[http://dx.doi.org/10.1007/s00018-018-2759-2] [PMID: 29417176]
[130]
Ying XX, Ying ZM, Xu L, Zhang WJ, Zhang CS. Amide alkaloids from Portulaca oleracea and their extraction and separation methods. CN106279305. (2017).
[131]
Xu L, Ying ZM, Wei WJ, Hao D, Wang H, Zhang WJ. A novel alkaloid from Portulaca oleracea L. Nat Prod Res 2017; 31(8): 902-8.
[http://dx.doi.org/10.1080/14786419.2016.1253081] [PMID: 27806650]
[132]
Ma LG, Wei RR, Liu WM, Sang ZP, Li T. A new alkaloid compound and its preparation method and application. CN106966969. (2017).
[133]
Wang KW, Ge YC. An aporphine alkaloid Illigerine A and its preparation and application. CN107043383. (2017).
[134]
Wang KW, Ge YC. An aporphine alkaloid Illigerine B and its preparation and application. CN107286172. (2017).
[135]
Wang KW, Ge YC. An aporphine alkaloid Laurodionine B and its preparation and application. CN107033156. (2017).
[136]
Ge YC, Zhang HJ, Wang KW, Fan XF. Aporphine Alkaloids from Illigera aromatica from Guangxi Province, China. Phytochemistry 2018; 154: 73-6.
[http://dx.doi.org/10.1016/j.phytochem.2018.06.017] [PMID: 30006090]