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Medicinal Chemistry

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ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

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Mini-Review Article

Insight on Structural Modification, Cytotoxic or Anti-Proliferative Activity, Structure-Activity Relationship of Berberine Derivatives

Author(s): Mengxuan Yin, Jiajia Mou*, Lili Sun*, Yanru Deng and Xiaoliang Ren

Volume 19, Issue 9, 2023

Published on: 28 April, 2023

Page: [823 - 837] Pages: 15

DOI: 10.2174/1573406419666230403120956

Price: $65

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Abstract

Berberine (BBR) is a quaternary ammonium alkaloid isolated from the Traditional Chinese Medicine Coptis chinensis. It possesses a plethora of pharmacological activities because its unique structure properties make it readily interact with macromolecules through π-π stacking and electrostatic interaction. Its anti-tumor effects are receiving more and more attention in recent years. Cytotoxicity and anti-proliferation are the important anti-tumor modes of BBR, which have been studied by many research groups.

This study aims to review the structural modifications of BBR and its cytotoxic derivatives. Also, to study the corresponding structure-activity relationship. BBR showed potential activities toward tumor cells, however, its modest activity and poor physicochemical properties hindered its application in clinical. Structural modification is a common and effective approach to improve BBR's cytotoxic or anti-proliferative activities.

The structural modifications of BBR, the cytotoxic or anti-proliferative activities of its derivatives, and the corresponding structure-activity relationship (SAR) were summarized in the review.

The concluded SAR of BBR derivatives with their cytotoxic or anti-proliferative activities will provide great prospects for the future anti-tumor drug design with BBR as the lead compound.

Keywords: Berberine, modification, derivative, anti-tumor effect, cytotoxic activity, anti-proliferative activity.

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[1]
Gaba, S.; Saini, A.; Singh, G.; Monga, V. An insight into the medicinal attributes of berberine derivatives: A review. Bioorg. Med. Chem., 2021, 38, 116143.
[http://dx.doi.org/10.1016/j.bmc.2021.116143] [PMID: 33848698]
[2]
Xu, X.; Yi, H.; Wu, J.; Kuang, T.; Zhang, J.; Li, Q.; Du, H.; Xu, T.; Jiang, G.; Fan, G. Therapeutic effect of berberine on metabolic diseases: Both pharmacological data and clinical evidence. Biomed. Pharmacother., 2021, 133, 110984.
[http://dx.doi.org/10.1016/j.biopha.2020.110984] [PMID: 33186794]
[3]
Hu, X.M.; Li, R.T.; Zhang, M.M.; Wu, K.Y.; Li, H.H.; Huang, N.H.; Sun, B.; Chen, J.X. Phenanthroline-linked berberine dimer and fluorophore-tagged DNA conjugate for the selective detection of microRNA-185: Experimental and molecular docking studies. Anal. Chim. Acta, 2019, 1051, 153-159.
[http://dx.doi.org/10.1016/j.aca.2018.11.022] [PMID: 30661612]
[4]
Avci, F.G.; Sayar, N.A.; Sariyar Akbulut, B. An OMIC approach to elaborate the antibacterial mechanisms of different alkaloids. Phytochemistry, 2018, 149, 123-131.
[http://dx.doi.org/10.1016/j.phytochem.2017.12.023] [PMID: 29494814]
[5]
Tong, Y.; Zhang, J.; Sun, N.; Wang, X.M.; Wei, Q.; Zhang, Y.; Huang, R.; Pu, Y.; Dai, H.; Ren, B.; Pei, G.; Song, F.; Zhu, G.; Wang, X.; Xia, X.; Chen, X.; Jiang, L.; Wang, S.; Ouyang, L.; Xie, N.; Zhang, B.; Jiang, Y.; Liu, X.; Calderone, R.; Bai, F.; Zhang, L.; Alterovitz, G. Berberine reverses multidrug resistance in Candida albicans by hijacking the drug efflux pump Mdr1p. Sci. Bull., 2021, 66(18), 1895-1905.
[http://dx.doi.org/10.1016/j.scib.2020.12.035] [PMID: 36654399]
[6]
Cecil, C.E.; Davis, J.M.; Cech, N.B.; Laster, S.M. Inhibition of H1N1 influenza A virus growth and induction of inflammatory mediators by the isoquinoline alkaloid berberine and extracts of goldenseal (Hydrastis canadensis). Int. Immunopharmacol., 2011, 11(11), 1706-1714.
[http://dx.doi.org/10.1016/j.intimp.2011.06.002] [PMID: 21683808]
[7]
Hung, T.C.; Jassey, A.; Liu, C.H.; Lin, C.J.; Lin, C.C.; Wong, S.H.; Wang, J.Y.; Yen, M.H.; Lin, L.T. Berberine inhibits hepatitis C virus entry by targeting the viral E2 glycoprotein. Phytomedicine, 2019, 53, 62-69.
[http://dx.doi.org/10.1016/j.phymed.2018.09.025] [PMID: 30668413]
[8]
Ma, J.; Chan, C.C.; Huang, W.C.; Kuo, M.L. Berberine inhibits pro-inflammatory cytokine-induced IL-6 and CCL11 production via modulation of STAT6 pathway in human bronchial epithelial cells. Int. J. Med. Sci., 2020, 17(10), 1464-1473.
[http://dx.doi.org/10.7150/ijms.45400] [PMID: 32624703]
[9]
Fu, K.; Wang, Z.; Cao, R. Berberine attenuates the inflammatory response by activating the Keap1/Nrf2 signaling pathway in bovine endometrial epithelial cells. Int. Immunopharmacol., 2021, 96, 107738.
[http://dx.doi.org/10.1016/j.intimp.2021.107738] [PMID: 33984720]
[10]
Di, S.; Han, L.; An, X.; Kong, R.; Gao, Z.; Yang, Y.; Wang, X.; Zhang, P.; Ding, Q.; Wu, H.; Wang, H.; Zhao, L.; Tong, X. In silico network pharmacology and in vivo analysis of berberine-related mechanisms against type 2 diabetes mellitus and its complications. J. Ethnopharmacol., 2021, 276, 114180.
[http://dx.doi.org/10.1016/j.jep.2021.114180] [PMID: 33957209]
[11]
Ye, L.; Liang, S.; Guo, C.; Yu, X.; Zhao, J.; Zhang, H.; Shang, W. Inhibition of M1 macrophage activation in adipose tissue by berberine improves insulin resistance. Life Sci., 2016, 166, 82-91.
[http://dx.doi.org/10.1016/j.lfs.2016.09.025] [PMID: 27702567]
[12]
Zhou, Y.; Cao, S.; Wang, Y.; Xu, P.; Yan, J.; Bin, W.; Qiu, F.; Kang, N. Berberine metabolites could induce low density lipoprotein receptor up-regulation to exert lipid-lowering effects in human hepatoma cells. Fitoterapia, 2014, 92, 230-237.
[http://dx.doi.org/10.1016/j.fitote.2013.11.010] [PMID: 24321576]
[13]
Hu, Y.; Ehli, E.A.; Kittelsrud, J.; Ronan, P.J.; Munger, K.; Downey, T.; Bohlen, K.; Callahan, L.; Munson, V.; Jahnke, M.; Marshall, L.L.; Nelson, K.; Huizenga, P.; Hansen, R.; Soundy, T.J.; Davies, G.E. Lipid-lowering effect of berberine in human subjects and rats. Phytomedicine, 2012, 19(10), 861-867.
[http://dx.doi.org/10.1016/j.phymed.2012.05.009] [PMID: 22739410]
[14]
Zhang, Y.; Liu, X.; Yu, M.; Xu, M.; Xiao, Y.; Ma, W.; Huang, L.; Li, X.; Ye, X. Berberine inhibits proliferation and induces G0/G1 phase arrest in colorectal cancer cells by downregulating IGF2BP3. Life Sci., 2020, 260, 118413.
[http://dx.doi.org/10.1016/j.lfs.2020.118413] [PMID: 32926933]
[15]
Ren, S.; Cai, Y.; Hu, S.; Liu, J.; Zhao, Y.; Ding, M.; Chen, X.; Zhan, L.; Zhou, X.; Wang, X. Berberine exerts anti-tumor activity in diffuse large B-cell lymphoma by modulating c-myc/CD47 axis. Biochem. Pharmacol., 2021, 188, 114576.
[http://dx.doi.org/10.1016/j.bcp.2021.114576] [PMID: 33930347]
[16]
Li, M.H.; Zhang, Y.J.; Yu, Y.H.; Yang, S.H.; Iqbal, J.; Mi, Q.Y.; Li, B.; Wang, Z.M.; Mao, W.X.; Xie, H.G.; Chen, S.L. Berberine improves pressure overload-induced cardiac hypertrophy and dysfunction through enhanced autophagy. Eur. J. Pharmacol., 2014, 728, 67-76.
[http://dx.doi.org/10.1016/j.ejphar.2014.01.061] [PMID: 24508518]
[17]
Salehi, S.; Filtz, T.M. Berberine possesses muscarinic agonist-like properties in cultured rodent cardiomyocytes. Pharmacol. Res., 2011, 63(4), 335-340.
[http://dx.doi.org/10.1016/j.phrs.2010.12.004] [PMID: 21168503]
[18]
Wang, L.; Deng, L.; Lin, N.; Shi, Y.; Chen, J.; Zhou, Y.; Chen, D.; Liu, S.; Li, C. Berberine inhibits proliferation and apoptosis of vascular smooth muscle cells induced by mechanical stretch via the PDI/ERS and MAPK pathways. Life Sci., 2020, 259, 118253.
[http://dx.doi.org/10.1016/j.lfs.2020.118253] [PMID: 32795536]
[19]
Hussien, H.M.; Abd-Elmegied, A.; Ghareeb, D.A.; Hafez, H.S.; Ahmed, H.E.A.; El-moneam, N.A. Neuroprotective effect of berberine against environmental heavy metals-induced neurotoxicity and Alzheimer’s-like disease in rats. Food Chem. Toxicol., 2018, 111, 432-444.
[http://dx.doi.org/10.1016/j.fct.2017.11.025] [PMID: 29170048]
[20]
Živančević, K.; Baralić, K.; Bozic, D.; Miljaković, E.A.; Djordjevic, A.B.; Ćurčić, M.; Bulat, Z.; Antonijević, B.; Bulat, P.; Đukić-Ćosić, D. Involvement of environmentally relevant toxic metal mixture in Alzheimer’s disease pathway alteration and protective role of berberine: Bioinformatics analysis and toxicogenomic screening. Food Chem. Toxicol., 2022, 161, 112839.
[http://dx.doi.org/10.1016/j.fct.2022.112839] [PMID: 35085532]
[21]
Wang, Y.; Liu, Y.; Du, X.; Ma, H.; Yao, J. The anti-cancer mechanisms of berberine: a review. Cancer Manag. Res., 2020, 12, 695-702.
[http://dx.doi.org/10.2147/CMAR.S242329] [PMID: 32099466]
[22]
Jin, Y.; Khadka, D.B.; Cho, W.J. Pharmacological effects of berberine and its derivatives: a patent update. Expert Opin. Ther. Pat., 2016, 26(2), 229-243.
[http://dx.doi.org/10.1517/13543776.2016.1118060] [PMID: 26610159]
[23]
Guamán Ortiz, L.; Lombardi, P.; Tillhon, M.; Scovassi, A. Berberine, an epiphany against cancer. Molecules, 2014, 19(8), 12349-12367.
[http://dx.doi.org/10.3390/molecules190812349] [PMID: 25153862]
[24]
Liang, K.W.; Yin, S.C.; Ting, C.T.; Lin, S.J.; Hsueh, C.M.; Chen, C.Y.; Hsu, S.L. Berberine inhibits platelet-derived growth factor induced growth and migration partly through an AMPK-dependent pathway in vascular smooth muscle cells. Eur. J. Pharmacol., 2008, 590(1-3), 343-354.
[http://dx.doi.org/10.1016/j.ejphar.2008.06.034] [PMID: 18590725]
[25]
Land, H.; Sampson, E.R.; McMurray, H.R. Methods and compositions related to synergistic responses to oncogenic mutations. U.S. patent AU2008307544A1, 2009.
[26]
Mazzini, S.; Bellucci, M.C.; Mondelli, R. Mode of binding of the cytotoxic alkaloid berberine with the double helix oligonucleotide d(AAGAATTCTT)2. Bioorg. Med. Chem., 2003, 11(4), 505-514.
[http://dx.doi.org/10.1016/S0968-0896(02)00466-2] [PMID: 12538015]
[27]
Kumar, G.S.; Das, S.; Bhadra, K.; Maiti, M. Protonated forms of poly[d(G-C)] and poly(dG).poly(dC) and Their interaction with berberine. Bioorg. Med. Chem., 2003, 11(23), 4861-4870.
[http://dx.doi.org/10.1016/j.bmc.2003.09.028] [PMID: 14604647]
[28]
Das, S.; Kumar, G.S.; Ray, A.; Maiti, M. Spectroscopic and thermodynamic studies on the binding of sanguinarine and berberine to triple and double helical DNA and RNA structures. J. Biomol. Struct. Dyn., 2003, 20(5), 703-713.
[http://dx.doi.org/10.1080/07391102.2003.10506887] [PMID: 12643773]
[29]
Parkinson, G.N.; Lee, M.P.H.; Neidle, S. Crystal structure of parallel quadruplexes from human telomeric DNA. Nature, 2002, 417(6891), 876-880.
[http://dx.doi.org/10.1038/nature755] [PMID: 12050675]
[30]
Franceschin, M.; Rossetti, L.; D’Ambrosio, A.; Schirripa, S.; Bianco, A.; Ortaggi, G.; Savino, M.; Schultes, C.; Neidle, S. Natural and synthetic G-quadruplex interactive berberine derivatives. Bioorg. Med. Chem. Lett., 2006, 16(6), 1707-1711.
[http://dx.doi.org/10.1016/j.bmcl.2005.12.001] [PMID: 16377184]
[31]
Wang, N.; Wang, X.; Tan, H.Y.; Li, S.; Tsang, C.; Tsao, S.W.; Feng, Y. Berberine suppresses cyclin D1 expression through proteasomal degradation in human hepatoma cells. Int. J. Mol. Sci., 2016, 17(11), 1899.
[http://dx.doi.org/10.3390/ijms17111899] [PMID: 27854312]
[32]
Qin, Y.; Pang, J.Y.; Chen, W.H.; Zhao, Z.Z.; Liu, L.; Jiang, Z.H. Inhibition of DNA topoisomerase I by natural and synthetic mono- and dimeric protoberberine alkaloids. Chem. Biodivers., 2007, 4(3), 481-487.
[http://dx.doi.org/10.1002/cbdv.200790040] [PMID: 17372950]
[33]
Samad, M.A.; Saiman, M.Z.; Abdul Majid, N.; Karsani, S.A.; Yaacob, J.S. Berberine inhibits telomerase activity and induces cell cycle arrest and telomere erosion in colorectal cancer cell line, HCT 116. Molecules, 2021, 26(2), 376.
[http://dx.doi.org/10.3390/molecules26020376] [PMID: 33450878]
[34]
Kim, S.; Lee, J.; You, D.; Jeong, Y.; Jeon, M.; Yu, J.; Kim, S.W.; Nam, S.J.; Lee, J.E. Berberine suppresses cell motility through downregulation of TGF-beta1 in triple negative breast cancer cells. Cell. Physiol. Biochem., 2018, 45(2), 795-807.
[http://dx.doi.org/10.1159/000487171] [PMID: 29414799]
[35]
Shen, M.; Zhang, Z.; Ratnam, M.; Dou, Q.P. The interplay of AMP-activated protein kinase and androgen receptor in prostate cancer cells. J. Cell. Physiol., 2014, 229(6), 688-695.
[http://dx.doi.org/10.1002/jcp.24494] [PMID: 24129850]
[36]
Fu, L.; Chen, W.; Guo, W.; Wang, J.; Tian, Y.; Shi, D.; Zhang, X.; Qiu, H.; Xiao, X.; Kang, T.; Huang, W.; Wang, S.; Deng, W. Berberine targets AP-2/hTERT, NF-κB/COX-2, HIF-1α/VEGF and cytochrome-c/caspase signaling to suppress human cancer cell growth. PLoS One, 2013, 8(7), e69240.
[http://dx.doi.org/10.1371/journal.pone.0069240]
[37]
Chatterjee, A.; Paul, S.; Bisht, B.; Bhattacharya, S.; Sivasubramaniam, S.; Paul, M.K. Advances in targeting the WNT/β-catenin signaling pathway in cancer. Drug Discov. Today, 2022, 27(1), 82-101.
[http://dx.doi.org/10.1016/j.drudis.2021.07.007] [PMID: 34252612]
[38]
Zhou, X.; Chen, M.; Zheng, Z.; Zhu, G.Y.; Jiang, Z.H.; Bai, L.P. Synthesis and evaluation of novel 12-aryl berberine analogues with hypoxia-inducible factor-1 inhibitory activity. RSC Advances, 2017, 7(43), 26921-26929.
[http://dx.doi.org/10.1039/C7RA02238G]
[39]
Fan, Y.; Ma, Z.; Zhao, L.; Wang, W.; Gao, M.; Jia, X.; Ouyang, H.; He, J. Anti-tumor activities and mechanisms of Traditional Chinese medicines formulas: A review. Biomed. Pharmacother., 2020, 132, 110820.
[http://dx.doi.org/10.1016/j.biopha.2020.110820] [PMID: 33035836]
[40]
England, K. 'Driscoll, C.O.; Cotter, T.G. ROS and protein oxidation in early stages of cytotoxic drug induced apoptosis. Free Radic. Res., 2006, 40(11), 1124-1137.
[http://dx.doi.org/10.1080/10715760600838209] [PMID: 17050166]
[41]
Liu, C.S.; Zheng, Y.R.; Zhang, Y.F.; Long, X.Y. Research progress on berberine with a special focus on its oral bioavailability. Fitoterapia, 2016, 109, 274-282.
[http://dx.doi.org/10.1016/j.fitote.2016.02.001] [PMID: 26851175]
[42]
Singh, S.; Pathak, N.; Fatima, E.; Negi, A.S. Plant isoquinoline alkaloids: Advances in the chemistry and biology of berberine. Eur. J. Med. Chem., 2021, 226, 113839.
[http://dx.doi.org/10.1016/j.ejmech.2021.113839] [PMID: 34536668]
[43]
Iwasa, K.; Moriyasu, M.; Yamori, T.; Turuo, T.; Lee, D.U.; Wiegrebe, W. In vitro cytotoxicity of the protoberberine-type alkaloids. J. Nat. Prod., 2001, 64(7), 896-898.
[http://dx.doi.org/10.1021/np000554f] [PMID: 11473418]
[44]
Ding, Y.; Ye, X.; Zhu, J.; Zhu, X.; Li, X. Synthesis of 8-alkyl-13-bromo-berberine hydrochloride derivatives and their effect on proliferation of human HepG2 cell line. Zhong Cao Yao, 2010, 41(11), 1765-1770.
[45]
Zhang, L.; Li, J.; Ma, F.; Yao, S.; Li, N.; Wang, J.; Wang, Y.; Wang, X.; Yao, Q. Synthesis and cytotoxicity evaluation of 13-n-alkyl berberine and palmatine analogues as anticancer agents. Molecules, 2012, 17(10), 11294-11302.
[http://dx.doi.org/10.3390/molecules171011294] [PMID: 23011273]
[46]
Li, Q.; He, W.; Zhang, L.; Zu, Y.; Zhu, Q.; Deng, X.; Zhao, T.; Gao, W.; Zhang, B. Synthesis, anticancer activities, antimicrobial activities and bioavailability of berberine-bile acid analogues. Lett. Drug Des. Discov., 2012, 9(6), 573-580.
[http://dx.doi.org/10.2174/157018012800673010]
[47]
Lo, C.Y.; Hsu, L.C.; Chen, M.S.; Lin, Y.J.; Chen, L.G.; Kuo, C.D.; Wu, J.Y. Synthesis and anticancer activity of a novel series of 9-O-substituted berberine derivatives: A lipophilic substitute role. Bioorg. Med. Chem. Lett., 2013, 23(1), 305-309.
[http://dx.doi.org/10.1016/j.bmcl.2012.10.098] [PMID: 23182088]
[48]
Chang, J.M.; Wu, J.Y.; Chen, S.H.; Chao, W.Y.; Chuang, H.H.; Kam, K.H.; Zhao, P.W.; Li, Y.Z.; Yen, Y.P.; Lee, Y.R. 9-O-Terpenyl-substituted berberrubine derivatives suppress tumor migration and increase anti-human non-small-cell lung cancer activity. Int. J. Mol. Sci., 2021, 22(18), 9864.
[http://dx.doi.org/10.3390/ijms22189864] [PMID: 34576028]
[49]
Lin, H.J.; Ho, J.H.; Tsai, L.C.; Yang, F.Y.; Yang, L.L.; Kuo, C.D.; Chen, L.G.; Liu, Y.W.; Wu, J.Y. Synthesis and in vitro photocytotoxicity of 9-/13-lipophilic substituted berberine derivatives as potential anticancer agents. Molecules, 2020, 25(3), 677.
[http://dx.doi.org/10.3390/molecules25030677] [PMID: 32033326]
[50]
Zhao, W.; Li, Y.; Li, Y.; Wang, Y.; Bi, C.; Shao, R.; Song, D. Synthesis and structure-activity relationship of 13-substituted berberine derivatives as anti-cancer agents. Zhongguo Yi Yao Dao Bao, 2013, 10(18), 17-20.
[51]
Li, Y.B.; Zhao, W.L.; Wang, Y.X.; Zhang, C.X.; Jiang, J.D.; Bi, C.W.; Tang, S.; Chen, R.X.; Shao, R.G.; Song, D.Q. Discovery, synthesis and biological evaluation of cycloprotoberberine derivatives as potential antitumor agents. Eur. J. Med. Chem., 2013, 68, 463-472.
[http://dx.doi.org/10.1016/j.ejmech.2013.07.026] [PMID: 24012683]
[52]
Bi, C.W.; Zhang, C.X.; Li, Y.B.; Zhao, W.L.; Shao, R.G.; Mei, L.; Song, D.Q. Synthesis and structure-activity relationship of cycloberberine as anti-cancer agent. Yao Xue Xue Bao, 2013, 48(12), 1800-1806.
[PMID: 24689237]
[53]
Albring, K.F.; Weidemüller, J.; Mittag, S.; Weiske, J.; Friedrich, K.; Geroni, M.C.; Lombardi, P.; Huber, O. Berberine acts as a natural inhibitor of Wnt/β-catenin signaling-Identification of more active 13-arylalkyl derivatives. Biofactors, 2013, 39(6), 652-662.
[http://dx.doi.org/10.1002/biof.1133] [PMID: 23982892]
[54]
Pierpaoli, E.; Arcamone, A.G.; Buzzetti, F.; Lombardi, P.; Salvatore, C.; Provinciali, M. Antitumor effect of novel berberine derivatives in breast cancer cells. Biofactors, 2013, 39(6), 672-679.
[http://dx.doi.org/10.1002/biof.1131] [PMID: 24000115]
[55]
Moasser, M.M. The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis. Oncogene, 2007, 26(45), 6469-6487.
[http://dx.doi.org/10.1038/sj.onc.1210477] [PMID: 17471238]
[56]
Ménard, S.; Pupa, S.M.; Campiglio, M.; Tagliabue, E. Biologic and therapeutic role of HER2 in cancer. Oncogene, 2003, 22(42), 6570-6578.
[http://dx.doi.org/10.1038/sj.onc.1206779] [PMID: 14528282]
[57]
Guamán Ortiz, L.M.; Tillhon, M.; Parks, M.; Dutto, I.; Prosperi, E.; Savio, M.; Arcamone, A.G.; Buzzetti, F.; Lombardi, P.; Scovassi, A.I. Multiple effects of berberine derivatives on colon cancer cells. BioMed Res. Int., 2014, 2014, 1-12.
[http://dx.doi.org/10.1155/2014/924585] [PMID: 25045712]
[58]
Guamán Ortiz, L.M.; Croce, A.L.; Aredia, F.; Sapienza, S.; Fiorillo, G.; Syeda, T.M.; Buzzetti, F.; Lombardi, P.; Scovassi, A.I. Effect of new berberine derivatives on colon cancer cells. Acta Biochim. Biophys. Sin., 2015, 47(10), 824-833.
[http://dx.doi.org/10.1093/abbs/gmv077] [PMID: 26341980]
[59]
Liu, C.; Liu, S.; Wang, Y.; Wang, S.; Zhang, J.; Li, S.; Qin, X.; Li, X.; Wang, K.; Zhou, Q. Synthesis, cytotoxicity, and DNA-binding property of berberine derivatives. Med. Chem. Res., 2014, 23(4), 1899-1907.
[http://dx.doi.org/10.1007/s00044-013-0796-9]
[60]
Jin, X.; Yan, T.H.; Yan, L.; Li, Q.; Wang, R.L.; Hu, Z.L.; Jiang, Y.Y.; Sun, Q.Y.; Cao, Y.B. Design, synthesis, and anticancer activity of novel berberine derivatives prepared via CuAAC “click” chemistry as potential anticancer agents. Drug Des. Devel. Ther., 2014, 8, 1047-1059.
[http://dx.doi.org/10.2147/DDDT.S63228] [PMID: 25120353]
[61]
Jin, X.; Yan, L.; Li, H.; Wang, R.L.; Hu, Z.L.; Jiang, Y.Y.; Cao, Y.B.; Yan, T.H.; Sun, Q.Y. Novel triazolyl berberine derivatives prepared via CuAAC click chemistry: synthesis, anticancer activity and structure-activity relationships. Anticancer. Agents Med. Chem., 2014, 15(1), 89-98.
[http://dx.doi.org/10.2174/1871520614666141203142012] [PMID: 25482720]
[62]
Pongkittiphan, V.; Chavasiri, W.; Supabphol, R. Antioxidant effect of berberine and its phenolic derivatives against human fibrosarcoma cells. Asian Pac. J. Cancer Prev., 2015, 16(13), 5371-5376.
[http://dx.doi.org/10.7314/APJCP.2015.16.13.5371] [PMID: 26225680]
[63]
Harris, I.S.; DeNicola, G.M. The complex interplay between antioxidants and ROS in cancer. Trends Cell Biol., 2020, 30(6), 440-451.
[http://dx.doi.org/10.1016/j.tcb.2020.03.002] [PMID: 32303435]
[64]
Hayes, J.D.; Dinkova-Kostova, A.T.; Tew, K.D. Oxidative stress in cancer. Cancer Cell, 2020, 38(2), 167-197.
[http://dx.doi.org/10.1016/j.ccell.2020.06.001] [PMID: 32649885]
[65]
Fu, S.; Xie, Y.; Tuo, J.; Wang, Y.; Zhu, W.; Wu, S.; Yan, G.; Hu, H. Discovery of mitochondria-targeting berberine derivatives as the inhibitors of proliferation, invasion and migration against rat C6 and human U87 glioma cells. Med. Chem. Comm., 2015, 6(1), 164-173.
[http://dx.doi.org/10.1039/C4MD00264D] [PMID: 26811742]
[66]
Mistry, B.; Keum, Y.S.; Kim, D.H. Synthesis, antioxidant and anticancer screenings of berberine–indole conjugates. Res. Chem. Intermed., 2016, 42(4), 3241-3256.
[http://dx.doi.org/10.1007/s11164-015-2208-x]
[67]
Mistry, B.M.; Patel, R.V.; Keum, Y.S.; Kim, D.H. Synthesis of 9-O-3-(1-piperazinyl/morpholinyl/piperidinyl)pentyl-berberines as Potential Antioxidant and Cytotoxic Agents. Anticancer. Agents Med. Chem., 2016, 16(6), 713-721.
[http://dx.doi.org/10.2174/1871520615666151009114759] [PMID: 26453450]
[68]
Mistry, B.; Keum, Y.S.; Kim, D.H. Synthesis and biological evaluation of berberine derivatives bearing 4-aryl-1-piperazine moieties. J. Chem. Res., 2015, 39(8), 470-474.
[http://dx.doi.org/10.3184/174751915X14381686689721]
[69]
Mistry, B.; Keum, Y.S.; Pandurangan, M.; Patel, R.V.; Kim, D.H. Synthesis of berberine-piperazine conjugates as potential antioxidant and cytotoxic agents. Med. Chem. Res., 2016, 25(11), 2461-2470.
[http://dx.doi.org/10.1007/s00044-016-1662-3]
[70]
Mistry, B.; Patel, R.V.; Keum, Y.S.; Kim, D.H. Evaluation of the biological potencies of newly synthesized berberine derivatives bearing benzothiazole moieties with substituted functionalities. J. Saudi Chem. Soc., 2017, 21(2), 210-219.
[http://dx.doi.org/10.1016/j.jscs.2015.11.002]
[71]
Mistry, B.; Keum, Y.S.; Noorzai, R.; Gansukh, E.; Kim, D.H. Synthesis of piperazine based N-Mannich bases of berberine and their antioxidant and anticancer evaluations. J. Indian Chem. Soc., 2016, 13(3), 531-539.
[http://dx.doi.org/10.1007/s13738-015-0762-1]
[72]
Mistry, B.; Patel, R.V.; Keum, Y.S.; Noorzai, R.; Gansukh, E.; Kim, D.H. Synthesis of Mannich base derivatives of berberine and evaluation of their anticancer and antioxidant effects. J. Chem. Res., 2016, 40(2), 73-77.
[http://dx.doi.org/10.3184/174751916X14525986827769]
[73]
Mistry, B.M.; Shin, H.S.; Keum, Y.S.; Kim, D.H.; Moon, S.H.; Kadam, A.A.; Shinde, S.K.; Patel, R.V.; Patel, R.V. Synthesis and evaluation of antioxidant and cytotoxicity of the N-Mannich base of berberine bearing benzothiazole moieties. Anticancer. Agents65651. Med. Chem., 2018, 17(12), 1652-1660.
[http://dx.doi.org/10.2174/1871520617666170710180549] [PMID: 28699489]
[74]
Mistry, B.; Patel, R.V.; Keum, Y.S.; Kim, D.H. Synthesis of N-Mannich bases of berberine linking piperazine moieties revealing anticancer and antioxidant effects. Saudi J. Biol. Sci., 2017, 24(1), 36-44.
[http://dx.doi.org/10.1016/j.sjbs.2015.09.005] [PMID: 28053569]
[75]
Wang, J.; Yang, T.; Chen, H.; Xu, Y.N.; Yu, L.F.; Liu, T.; Tang, J.; Yi, Z.; Yang, C.G.; Xue, W.; Yang, F. The synthesis and antistaphylococcal activity of 9, 13-disubstituted berberine derivatives. Eur. J. Med. Chem., 2017, 127, 424-433.
[http://dx.doi.org/10.1016/j.ejmech.2017.01.012] [PMID: 28092858]
[76]
Wang, Z.C.; Wang, J.; Chen, H.; Tang, J.; Bian, A.W.; Liu, T.; Yu, L.F.; Yi, Z.; Yang, F. Synthesis and anticancer activity of novel 9,13-disubstituted berberine derivatives. Bioorg. Med. Chem. Lett., 2020, 30(2), 126821.
[http://dx.doi.org/10.1016/j.bmcl.2019.126821] [PMID: 31812467]
[77]
Fukumura, D.; Kashiwagi, S.; Jain, R.K. The role of nitric oxide in tumour progression. Nat. Rev. Cancer, 2006, 6(7), 521-534.
[http://dx.doi.org/10.1038/nrc1910] [PMID: 16794635]
[78]
Zhou, L.; Wang, Y.; Tian, D.; Yang, J.; Yang, Y.Z. Decreased levels of nitric oxide production and nitric oxide synthase-2 expression are associated with the development and metastasis of hepatocellular carcinoma. Mol. Med. Rep., 2012, 6(6), 1261-1266.
[http://dx.doi.org/10.3892/mmr.2012.1096] [PMID: 23007408]
[79]
Zhou, L.; Zhang, H.; Wu, J. Effects of nitric oxide on the biological behavior of HepG2 human hepatocellular carcinoma cells. Exp. Ther. Med., 2016, 11(5), 1875-1880.
[http://dx.doi.org/10.3892/etm.2016.3128] [PMID: 27168820]
[80]
Fang, L.; Feng, M.; Chen, F.; Liu, X.; Shen, H.; Zhao, J.; Gou, S. Oleanolic acid-NO donor-platinum(II) trihybrid molecules: Targeting cytotoxicity on hepatoma cells with combined action mode and good safety. Bioorg. Med. Chem., 2016, 24(19), 4611-4619.
[http://dx.doi.org/10.1016/j.bmc.2016.07.066] [PMID: 27501909]
[81]
Hutchens, S.; Manevich, Y.; He, L.; Tew, K.D.; Townsend, D.M. Cellular resistance to a nitric oxide releasing glutathione S-transferase P-activated prodrug, PABA/NO. Invest. New Drugs, 2011, 29(5), 719-729.
[http://dx.doi.org/10.1007/s10637-010-9407-5] [PMID: 20232108]
[82]
Chen, J.; Wang, T.; Xu, S.; Lin, A.; Yao, H.; Xie, W.; Zhu, Z.; Xu, J. Design, synthesis and biological evaluation of novel nitric oxide-donating protoberberine derivatives as antitumor agents. Eur. J. Med. Chem., 2017, 132, 173-183.
[http://dx.doi.org/10.1016/j.ejmech.2017.03.027] [PMID: 28359045]
[83]
Xiao, D.; He, F.; Peng, D.; Zou, M.; Peng, J.; Liu, P.; Liu, Y.; Liu, Z. Synthesis and anticancer activity of 9-O-pyrazole alkyl substituted berberine derivatives. Anticancer. Agents Med. Chem., 2019, 18(11), 1639-1648.
[http://dx.doi.org/10.2174/1871520618666180717121208] [PMID: 30014806]
[84]
Jiang, X.; Zhang, N. Synthesis and evaluation antimicrobial activity and cytotoxic activity of 9-O-benzyl group berberine and 3-O-benzyl group jatrorrhizin derivatives. Mudanjiang Shi Fan Xue Yuan Xue Bao, 2018, 102, 51-55.
[85]
Jiang, X.; Liu, J.; Li, H.; Zhang, W.; Luo, H. Synthesis and physiological activity of novel berberine derivatives. Zhongguo Shiyan Fangjixue Zazhi, 2019, 25(23), 156-164.
[86]
Milata, V.; Svedova, A.; Barbierikova, Z.; Holubkova, E.; Cipakova, I.; Cholujova, D.; Jakubikova, J.; Panik, M.; Jantova, S.; Brezova, V.; Cipak, L. Synthesis and anticancer activity of novel 9-O-substituted berberine derivatives. Int. J. Mol. Sci., 2019, 20(9), 2169.
[http://dx.doi.org/10.3390/ijms20092169] [PMID: 31052469]
[87]
Wang, R.; Rostyslav, S.; Li, X.; Lin, H.; Zhang, X.; Zhang, S.; Liu, K.; Wang, L. Synthetic and antitumor comparison of 9-O-alkylated and carbohydrate-modified berberine derivatives. J. Indian Chem. Soc., 2020, 17(12), 3251-3260.
[http://dx.doi.org/10.1007/s13738-020-01985-0]
[88]
Wang, L.; Yang, X.; Li, X.; Stoika, R.; Wang, X.; Lin, H.; Ma, Y.; Wang, R.; Liu, K. Synthesis of hydrophobically modified berberine derivatives with high anticancer activity through modulation of the MAPK pathway. New J. Chem., 2020, 44(33), 14024-14034.
[http://dx.doi.org/10.1039/D0NJ01645D]
[89]
Mari, G.; De Crescentini, L.; Benedetti, S.; Palma, F.; Santeusanio, S.; Mantellini, F. Synthesis of new dihydroberberine and tetrahydroberberine analogues and evaluation of their antiproliferative activity on NCI-H1975 cells. Beilstein J. Org. Chem., 2020, 16, 1606-1616.
[http://dx.doi.org/10.3762/bjoc.16.133] [PMID: 32704327]
[90]
Wang, B.; Deng, A.J.; Li, Z.H.; Wang, N.; Qin, H.L. Syntheses and structure-activity relationships in growth inhibition activity against human cancer cell lines of 12 substituted berberine derivatives. Molecules, 2020, 25(8), 1871.
[http://dx.doi.org/10.3390/molecules25081871] [PMID: 32325679]

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