Generic placeholder image

Mini-Reviews in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Review Article

A Review on Recent Developments in the Anticancer Potential of Oleanolic Acid and its Analogs (2017-2020)

Author(s): Nidhi Gupta*

Volume 22, Issue 4, 2022

Published on: 04 January, 2022

Page: [600 - 616] Pages: 17

DOI: 10.2174/1389557521666210810153627

Price: $65

Abstract

Oleanolic acid (OA) is a pentacyclic triterpenoid class of natural products that possess a broad range of biological activities, specifically anticancer activities. Considering the anticancer potential of OA, a large number of analogs have been prepared by several researchers through modifications at C-3, C-12, and C-28 -COOH to develop potent anticancer agents with improved cytotoxicity and pharmaceutical properties. Some of the synthesized derivatives have been assessed in clinical trials also. This review summarizes the most recent synthetic and biological efforts in the development of oleanolic acid and its analogs during the period from 2017 to 2020. Reports published during this period revealed that both OA and its analogs possess a remarkable potential for the development of effective anticancer agents along with several others, such as anti-inflammatory, anti-viral, antimicrobial, and anti-diabetic agents.

Keywords: Oleanolic acid, derivatives, anticancer, anti-inflammatory, anti-diabetic, anti-viral.

Graphical Abstract
[1]
Sciacovelli, M.; Schmidt, C.; Maher, E.R.; Frezza, C. Metabolic drivers in hereditary cancer syndromes. Annu. Rev. Cancer Biol., 2020, 4, 77-97.
[http://dx.doi.org/10.1146/annurev-cancerbio-030419-033612]
[2]
Cragg, G.M.; Kingston, D.G.; Newman, D.J., Eds.; Anticancer agents from natural products; CRC press, 2011.
[http://dx.doi.org/10.1201/b11185]
[3]
Liu, W.; Li, Q.; Hu, J.; Wang, H.; Xu, F.; Bian, Q. Application of natural products derivatization method in the design of targeted anticancer agents from 2000 to 2018. Bioorg. Med. Chem., 2019, 27(23)115150
[http://dx.doi.org/10.1016/j.bmc.2019.115150] [PMID: 31635893]
[4]
Butler, M.S.; Robertson, A.A.; Cooper, M.A. Natural product and natural product derived drugs in clinical trials. Nat. Prod. Rep., 2014, 31(11), 1612-1661.
[http://dx.doi.org/10.1039/C4NP00064A] [PMID: 25204227]
[5]
Xu, R.; Fazio, G.C.; Matsuda, S.P. On the origins of triterpenoid skeletal diversity. Phytochemistry, 2004, 65(3), 261-291.
[http://dx.doi.org/10.1016/j.phytochem.2003.11.014] [PMID: 14751299]
[6]
Sheng, H.; Sun, H. Synthesis, biology and clinical significance of pentacyclic triterpenes: A multi-target approach to prevention and treatment of metabolic and vascular diseases. Nat. Prod. Rep., 2011, 28(3), 543-593.
[http://dx.doi.org/10.1039/c0np00059k] [PMID: 21290067]
[7]
Hussain, H.; Green, I.R.; Ali, I.; Khan, I.A.; Ali, Z.; Al-Sadi, A.M.; Ahmed, I. Ursolic acid derivatives for pharmaceutical use: A patent review (2012-2016). Expert Opin. Ther. Pat., 2017, 27(9), 1061-1072.
[http://dx.doi.org/10.1080/13543776.2017.1344219] [PMID: 28637397]
[8]
Salvador, J.A.R.; Leal, A.S.; Valdeira, A.S.; Gonçalves, B.M.F.; Alho, D.P.S.; Figueiredo, S.A.C.; Silvestre, S.M.; Mendes, V.I.S. Oleanane-, ursane-, and quinone methide friedelane-type triterpenoid derivatives: Recent advances in cancer treatment. Eur. J. Med. Chem., 2017, 142, 95-130.
[http://dx.doi.org/10.1016/j.ejmech.2017.07.013] [PMID: 28754470]
[9]
Liu, J. Pharmacology of oleanolic acid and ursolic acid. J. Ethnopharmacol., 1995, 49(2), 57-68.
[http://dx.doi.org/10.1016/0378-8741(95)90032-2] [PMID: 8847885]
[10]
Ayeleso, T.B.; Matumba, M.G.; Mukwevho, E. Oleanolic acid and its derivatives: Biological activities and therapeutic potential in chronic diseases. Molecules, 2017, 22(11), 1915.
[http://dx.doi.org/10.3390/molecules22111915] [PMID: 29137205]
[11]
Jäger, S.; Trojan, H.; Kopp, T.; Laszczyk, M.N.; Scheffler, A. Pentacyclic triterpene distribution in various plants - rich sources for a new group of multi-potent plant extracts. Molecules, 2009, 14(6), 2016-2031.
[http://dx.doi.org/10.3390/molecules14062016] [PMID: 19513002]
[12]
Pollier, J.; Goossens, A. Oleanolic acid. Phytochemistry, 2012, 77, 10-15.
[http://dx.doi.org/10.1016/j.phytochem.2011.12.022] [PMID: 22377690]
[13]
Lu, C.; Tang, Z.; Liu, C.; Ma, X. Surface molecularly imprinted polymers prepared by two-step precipitation polymerization for the selective extraction of oleanolic acid from grape pomace extract. J. Sep. Sci., 2018, 41(17), 3496-3502.
[http://dx.doi.org/10.1002/jssc.201800474] [PMID: 30027558]
[14]
Cláudio, A.F.M.; Cognigni, A.; de Faria, E.L.P.; Silvestre, A.J.D.; Zirbs, R.; Freire, M.G.; Bica, K. Valorization of olive tree leaves: Extraction of oleanolic acid using aqueous solutions of surface-active ionic liquids. Separ. Purif. Tech., 2018, 204, 30-37.
[http://dx.doi.org/10.1016/j.seppur.2018.04.042] [PMID: 30319309]
[15]
Xie, P.; Huang, L.; Zhang, C.; Deng, Y.; Wang, X.; Cheng, J. Enhanced extraction of hydroxytyrosol, maslinic acid and oleanolic acid from olive pomace: Process parameters, kinetics and thermodynamics, and greenness assessment. Food Chem., 2019, 276, 662-674.
[http://dx.doi.org/10.1016/j.foodchem.2018.10.079] [PMID: 30409646]
[16]
Xia, E.Q.; Yu, Y.Y.; Xu, X.R.; Deng, G.F.; Guo, Y.J.; Li, H.B. Ultrasound-assisted extraction of oleanolic acid and ursolic acid from Ligustrum lucidum Ait. Ultrason. Sonochem., 2012, 19(4), 772-776.
[http://dx.doi.org/10.1016/j.ultsonch.2011.11.014] [PMID: 22197019]
[17]
Xia, E.Q.; Wang, B.W.; Xu, X.R.; Zhu, L.; Song, Y.; Li, H.B. Microwave-assisted extraction of oleanolic acid and ursolic acid from Ligustrum lucidum Ait. Int. J. Mol. Sci., 2011, 12(8), 5319-5329.
[http://dx.doi.org/10.3390/ijms12085319] [PMID: 21954361]
[18]
Wang, C.; Wang, X.; Zhao, S.; Zuo, G.; Xu, M.; Tong, S. Liquid chromatographic and liquid-liquid chromatographic separation of structural isomeric oleanolic acid and ursolic acid using hydroxypropyl-β-cyclodextrin as additive. J. Chromatogr. A, 2020.1625461332
[http://dx.doi.org/10.1016/j.chroma.2020.461332] [PMID: 32709358]
[19]
Ren, T.; Xu, Z. Study of isomeric pentacyclic triterpene acids in traditional Chinese medicine of Forsythiae Fructus and their binding constants with β-cyclodextrin by capillary electrophoresis. Electrophoresis, 2018, 39(7), 1006-1013.
[http://dx.doi.org/10.1002/elps.201700408] [PMID: 29315662]
[20]
Yang, Y.C.; Wei, M.C.; Huang, T.C. Optimisation of an ultrasound-assisted extraction followed by RP-HPLC separation for the simultaneous determination of oleanolic acid, ursolic acid and oridonin content in Rabdosia rubescens. Phytochem. Anal., 2012, 23(6), 627-636.
[http://dx.doi.org/10.1002/pca.2365] [PMID: 22706975]
[21]
Shanmugam, M.K.; Dai, X.; Kumar, A.P.; Tan, B.K.; Sethi, G.; Bishayee, A. Oleanolic acid and its synthetic derivatives for the prevention and therapy of cancer: Preclinical and clinical evidence. Cancer Lett., 2014, 346(2), 206-216.
[http://dx.doi.org/10.1016/j.canlet.2014.01.016] [PMID: 24486850]
[22]
Kim, G.J.; Jo, H.J.; Lee, K.J.; Choi, J.W.; An, J.H. Oleanolic acid induces p53-dependent apoptosis via the ERK/JNK/AKT pathway in cancer cell lines in prostatic cancer xenografts in mice. Oncotarget, 2018, 9(41), 26370-26386.
[http://dx.doi.org/10.18632/oncotarget.25316] [PMID: 29899865]
[23]
Potočnjak, I.; Šimić, L.; Vukelić, I.; Domitrović, R. Oleanolic acid attenuates cisplatin-induced nephrotoxicity in mice and chemosensitizes human cervical cancer cells to cisplatin cytotoxicity. Food Chem. Toxicol., 2019.132110676
[http://dx.doi.org/10.1016/j.fct.2019.110676] [PMID: 31306688]
[24]
Edathara, P.M.; Chintalapally, S.; Makani, V.K.K.; Pant, C.; Yerramsetty, S.D.; Rao, M.; Bhadra, M.P. Inhibitory role of oleanolic acid and esculetin in HeLa cells involve multiple signaling pathways. Gene, 2021.771145370
[http://dx.doi.org/10.1016/j.gene.2020.145370] [PMID: 33346097]
[25]
Kayouka, M.; Hamade, A.; Saliba, E.; Najjar, F.; Landy, D.; Greige-Gerges, H. P-glycoprotein modulates oleanolic acid effects in hepatocytes cancer cells and zebrafish embryos. Chem. Biol. Interact., 2020.315108892
[http://dx.doi.org/10.1016/j.cbi.2019.108892] [PMID: 31704064]
[26]
Li, Y.; Xu, Q.; Yang, W.; Wu, T.; Lu, X. Oleanolic acid reduces aerobic glycolysis-associated proliferation by inhibiting yes-associated protein in gastric cancer cells. Gene, 2019.712143956
[http://dx.doi.org/10.1016/j.gene.2019.143956] [PMID: 31271843]
[27]
Castrejón-Jiménez, N.S.; Leyva-Paredes, K.; Baltierra-Uribe, S.L.; Castillo-Cruz, J.; Campillo-Navarro, M.; Hernández-Pérez, A.D.; Luna-Angulo, A.B.; Chacón-Salinas, R.; Coral-Vázquez, R.M.; Estrada-García, I.; Sánchez-Torres, L.E.; Torres-Torres, C.; García-Pérez, B.E. Ursolic and oleanolic acids induce mitophagy in a549 human lung cancer cells. Molecules, 2019, 24(19), 3444.
[http://dx.doi.org/10.3390/molecules24193444] [PMID: 31547522]
[28]
Niu, G.; Sun, L.; Pei, Y.; Wang, D. Oleanolic acid inhibits colorectal cancer angiogenesis by blocking the VEGFR2 signaling pathway.Anti-Cancer Agents Med. Chem. (Formerly Current Medicinal Chemistry-Anti-Cancer Agents),, 2018, 18(4), 583-590.
[29]
Wang, L.; Wang, J.; Cao, Y.; Li, W.; Wang, Y.; Xu, J.; Xu, G. Molecular evidence for better efficacy of hypocrellin A and oleanolic acid combination in suppression of HCC growth. Eur. J. Pharmacol., 2019, 842, 281-290.
[http://dx.doi.org/10.1016/j.ejphar.2018.10.042] [PMID: 30391347]
[30]
Liese, J.; Hinrichs, T.M.; Lange, M.; Fulda, S. Cotreatment with sorafenib and oleanolic acid induces reactive oxygen species-dependent and mitochondrial-mediated apoptotic cell death in hepatocellular carcinoma cells. Anticancer Drugs, 2019, 30(3), 209-217.
[http://dx.doi.org/10.1097/CAD.0000000000000750] [PMID: 30640794]
[31]
Sarfraz, M.; Afzal, A.; Raza, S.M.; Bashir, S.; Madni, A.; Khan, M.W.; Ma, X.; Xiang, G. Liposomal co-delivered oleanolic acid attenuates doxorubicin-induced multi-organ toxicity in hepatocellular carcinoma. Oncotarget, 2017, 8(29), 47136-47153.
[http://dx.doi.org/10.18632/oncotarget.17559] [PMID: 28525367]
[32]
Duan, L.; Yang, Z.; Jiang, X.; Zhang, J.; Guo, X. Oleanolic acid inhibits cell proliferation migration and invasion and induces SW579 thyroid cancer cell line apoptosis by targeting forkhead transcription factor A. Anticancer Drugs, 2019, 30(8), 812-820.
[http://dx.doi.org/10.1097/CAD.0000000000000777] [PMID: 30882397]
[33]
Peng, X.P.; Li, X.H.; Li, Y.; Huang, X.T.; Luo, Z.Q. The protective effect of oleanolic acid on NMDA-induced MLE-12 cells apoptosis and lung injury in mice by activating SIRT1 and reducing NF-κB acetylation. Int. Immunopharmacol., 2019, 70, 520-529.
[http://dx.doi.org/10.1016/j.intimp.2019.03.018] [PMID: 30901738]
[34]
Wang, J.L.; Ren, C.H.; Feng, J.; Ou, C.H.; Liu, L. Oleanolic acid inhibits mouse spinal cord injury through suppressing inflammation and apoptosis via the blockage of p38 and JNK MAPKs. Biomed. Pharmacother., 2020.123109752
[http://dx.doi.org/10.1016/j.biopha.2019.109752] [PMID: 31924596]
[35]
Dong, S.Q.; Wang, S.S.; Zhu, J.X.; Mu, R.H.; Li, C.F.; Geng, D.; Liu, Q.; Yi, L.T. Oleanolic acid decreases SGK1 in the hippocampus in corticosterone-induced mice. Steroids, 2019.149108419
[http://dx.doi.org/10.1016/j.steroids.2019.05.011] [PMID: 31153932]
[36]
Lin, K.; Sze, S.C.W.; Liu, B.; Zhang, Z.; Zhang, Z.; Zhu, P.; Wang, Y.; Deng, Q.; Yung, K.K.L.; Zhang, S. 20 (S)-protopanaxadiol and oleanolic acid ameliorate cognitive deficits in APP/PS1 transgenic mice by enhancing hippocampal neurogenesis. J. Ginseng Res., 2020.
[http://dx.doi.org/10.1016/j.jgr.2020.07.003] [PMID: 33841013]
[37]
Soares, I.C.R.; Santos, S.A.A.R.; Coelho, R.F.; Alves, Y.A.; Vieira-Neto, A.E.; Tavares, K.C.S.; Magalhaes, F.E.A.; Campos, A.R. Oleanolic acid promotes orofacial antinociception in adult zebrafish (Danio rerio) through TRPV1 receptors. Chem. Biol. Interact., 2019, 299, 37-43.
[http://dx.doi.org/10.1016/j.cbi.2018.11.018] [PMID: 30496739]
[38]
Loza-Rodríguez, H.; Estrada-Soto, S.; Alarcón-Aguilar, F.J.; Huang, F.; Aquino-Jarquín, G.; Fortis-Barrera, Á.; Giacoman-Martínez, A.; Almanza-Pérez, J.C. Oleanolic acid induces a dual agonist action on PPARγ/α and GLUT4 translocation: A pentacyclic triterpene for dyslipidemia and type 2 diabetes. Eur. J. Pharmacol., 2020.883173252
[http://dx.doi.org/10.1016/j.ejphar.2020.173252] [PMID: 32534078]
[39]
Xie, B.P.; Shi, L.Y.; Li, J.P.; Zeng, Y.; Liu, W.; Tang, S.Y.; Jia, L.J.; Zhang, J.; Gan, G.X. Oleanolic acid inhibits RANKL-induced osteoclastogenesis via ER alpha/miR-503/RANK signaling pathway in RAW264.7 cells. Biomed. Pharmacother., 2019.117109045
[http://dx.doi.org/10.1016/j.biopha.2019.109045] [PMID: 31176167]
[40]
Zhao, D.; Li, X.; Zhao, Y.; Qiao, P.; Tang, D.; Chen, Y.; Xue, C.; Li, C.; Liu, S.; Wang, J.; Lu, S.; Shi, Q.; Zhang, Y.; Dong, Y.; Wang, Y.; Shu, B.; Feng, X. Oleanolic acid exerts bone protective effects in ovariectomized mice by inhibiting osteoclastogenesis. J. Pharmacol. Sci., 2018, 137(1), 76-85.
[http://dx.doi.org/10.1016/j.jphs.2018.03.007] [PMID: 29703642]
[41]
Ding, H.; Hu, X.; Xu, X.; Zhang, G.; Gong, D. Inhibitory mechanism of two allosteric inhibitors, oleanolic acid and ursolic acid on α-glucosidase. Int. J. Biol. Macromol., 2018, 107(Pt B), 1844-1855.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.10.040] [PMID: 29030193]
[42]
Su, S.; Wu, G.; Cheng, X.; Fan, J.; Peng, J.; Su, H.; Xu, Z.; Cao, M.; Long, Z.; Hao, Y.; Li, G.; Li, S.; Hai, C.; Wang, X. Oleanolic acid attenuates PCBs-induced adiposity and insulin resistance via HNF1b-mediated regulation of redox and PPARγ signaling. Free Radic. Biol. Med., 2018, 124, 122-134.
[http://dx.doi.org/10.1016/j.freeradbiomed.2018.06.003] [PMID: 29879443]
[43]
Senathilake, K.S.; Karunanayake, E.H.; Samarakoon, S.R.; Tennekoon, K.H.; de Silva, E.D.; Adhikari, A. Oleanolic acid from antifilarial triterpene saponins of Dipterocarpus zeylanicus induces oxidative stress and apoptosis in filarial parasite Setaria digitata in vitro. Exp. Parasitol., 2017, 177, 13-21.
[http://dx.doi.org/10.1016/j.exppara.2017.03.007] [PMID: 28351683]
[44]
Han, Y.W.; Liu, X.J.; Zhao, Y.; Li, X.M. Role of Oleanolic acid in maintaining BBB integrity by targeting p38MAPK/VEGF/Src signaling pathway in rat model of subarachnoid hemorrhage. Eur. J. Pharmacol., 2018, 839, 12-20.
[http://dx.doi.org/10.1016/j.ejphar.2018.09.018] [PMID: 30240794]
[45]
Wang, S.; Du, L.B.; Jin, L.; Wang, Z.; Peng, J.; Liao, N.; Zhao, Y.Y.; Zhang, J.L.; Pauluhn, J.; Hai, C.X.; Wang, X.; Li, W.L. Nano-oleanolic acid alleviates metabolic dysfunctions in rats with high fat and fructose diet. Biomed. Pharmacother., 2018, 108, 1181-1187.
[http://dx.doi.org/10.1016/j.biopha.2018.09.150] [PMID: 30372819]
[46]
Gupta, N.; Rath, S.K.; Singh, J.; Qayum, A.; Singh, S.; Sangwan, P.L. Synthesis of novel benzylidene analogues of betulinic acid as potent cytotoxic agents. Eur. J. Med. Chem., 2017, 135, 517-530.
[http://dx.doi.org/10.1016/j.ejmech.2017.04.062] [PMID: 28500966]
[47]
Borella, R.; Forti, L.; Gibellini, L.; De Gaetano, A.; De Biasi, S.; Nasi, M.; Cossarizza, A.; Pinti, M. Synthesis and anticancer activity of CDDO and CDDO-Me, two derivatives of natural triterpenoids. Molecules, 2019, 24(22), 4097.
[http://dx.doi.org/10.3390/molecules24224097] [PMID: 31766211]
[48]
Wang, S.S.; Zhang, Q.L.; Chu, P.; Kong, L.Q.; Li, G.Z.; Li, Y.Q.; Yang, L.; Zhao, W.J.; Guo, X.H.; Tang, Z.Y. Synthesis and antitumor activity of α,β-unsaturated carbonyl moiety- containing oleanolic acid derivatives targeting PI3K/AKT/mTOR signaling pathway. Bioorg. Chem., 2020.101104036
[http://dx.doi.org/10.1016/j.bioorg.2020.104036] [PMID: 32629283]
[49]
Fontana, G.; Bruno, M.; Notarbartolo, M.; Labbozzetta, M.; Poma, P.; Spinella, A.; Rosselli, S. Cytotoxicity of oleanolic and ursolic acid derivatives toward hepatocellular carcinoma and evaluation of NF-κB involvement. Bioorg. Chem., 2019.90103054
[http://dx.doi.org/10.1016/j.bioorg.2019.103054] [PMID: 31212180]
[50]
Krajka-Kuźniak, V.; Bednarczyk-Cwynar, B.; Narożna, M.; Szaefer, H.; Baer-Dubowska, W. Morpholide derivative of the novel oleanolic oxime and succinic acid conjugate diminish the expression and activity of NF-κB and STATs in human hepatocellular carcinoma cells. Chem. Biol. Interact., 2019.311108786
[http://dx.doi.org/10.1016/j.cbi.2019.108786] [PMID: 31401087]
[51]
Krajka-Kuźniak, V.; Bednarczyk-Cwynar, B.; Paluszczak, J.; Szaefer, H.; Narożna, M.; Zaprutko, L.; Baer-Dubowska, W. Oleanolic acid oxime derivatives and their conjugates with aspirin modulate the NF-κB-mediated transcription in HepG2 hepatoma cells. Bioorg. Chem., 2019.93103326
[http://dx.doi.org/10.1016/j.bioorg.2019.103326] [PMID: 31586705]
[52]
Narożna, M.; Krajka-Kuźniak, V.; Kleszcz, R.; Bednarczyk-Cwynar, B.; Szaefer, H.; Baer-Dubowska, W. Activation of the Nrf2 response by oleanolic acid oxime morpholide (3-hydroxyiminoolean-12-en-28-oic acid morpholide) is associated with its ability to induce apoptosis and inhibit proliferation in HepG2 hepatoma cells. Eur. J. Pharmacol., 2020.883173307
[http://dx.doi.org/10.1016/j.ejphar.2020.173307] [PMID: 32668287]
[53]
Wang, R.; Yang, W.; Fan, Y.; Dehaen, W.; Li, Y.; Li, H.; Wang, W.; Zheng, Q.; Huai, Q. Design and synthesis of the novel oleanolic acid-cinnamic acid ester derivatives and glycyrrhetinic acid-cinnamic acid ester derivatives with cytotoxic properties. Bioorg. Chem., 2019.88102951
[http://dx.doi.org/10.1016/j.bioorg.2019.102951] [PMID: 31054427]
[54]
Chouaïb, K.; Romdhane, A.; Delemasure, S.; Dutartre, P.; Elie, N.; Touboul, D.; Jannet, H.B. Regiospecific synthesis by copper-and ruthenium-catalyzed azide–alkyne 1, 3-dipolar cycloaddition, anticancer and anti-inflammatory activities of oleanolic acid triazole derivatives. Arab. J. Chem., 2019, 12(8), 3732-3742.
[http://dx.doi.org/10.1016/j.arabjc.2015.12.013]
[55]
Zou, Y.; Yan, C.; Liu, J.C.; Huang, Z.J. Synthesis and anti-hepatocellular carcinoma activity of novel O2-vinyl diazeniumdiolate-based nitric oxide-releasing derivatives of oleanolic acid. Chin. J. Nat. Med., 2017, 15(12), 0928-0937.
[56]
Meng, Y.Q.; Kuai, Z.Y.; Zhan, S.W.; Li, C.L.; Chen, H.R. Design, synthesis, and antitumor activity of oleanolic acid derivatives. J. Asian Nat. Prod. Res., 2019, 21(7), 633-651.
[http://dx.doi.org/10.1080/10286020.2018.1464560] [PMID: 29733221]
[57]
Bednarczyk-Cwynar, B.; Ruszkowskp, P.; Atamanyuk, D.; Lesyk, R.; Zaprutko, L. Hybrids of oleanolic acid with norbornene-2, 3-dicarboximide-N-carboxylic acids as potential anticancer agents. Acta Pol. Pharm., 2017, 74(3), 827-835.
[PMID: 29513952]
[58]
Chu, P.; Li, H.; Luo, R.; Ahsan, A.; Qaed, E.; Shopit, A.; Ma, X.; Lin, Y.; Peng, J.; Zhang, J.; Wang, S.; Tang, Z. Oleanolic acid derivative SZC014 inhibit cell proliferation and induce apoptosis of human breast cancer cells in a ROS-dependent way. Neoplasma, 2017, 64(5), 681-692.
[http://dx.doi.org/10.4149/neo_2017_505] [PMID: 28592114]
[59]
Mbaveng, A.T.; Chi, G.F.; Bonsou, I.N.; Abdelfatah, S.; Tamfu, A.N.; Yeboah, E.M.O.; Kuete, V.; Efferth, T. N-acetylglycoside of oleanolic acid (aridanin) displays promising cytotoxicity towards human and animal cancer cells, inducing apoptotic, ferroptotic and necroptotic cell death. Phytomedicine, 2020.76153261
[http://dx.doi.org/10.1016/j.phymed.2020.153261] [PMID: 32559584]
[60]
Lin, Y.Y.; Chan, S.H.; Juang, Y.P.; Hsiao, H.M.; Guh, J.H.; Liang, P.H. Design, synthesis and cytotoxic activity of N-Modified oleanolic saponins bearing A glucosamine. Eur. J. Med. Chem., 2018, 143, 1942-1958.
[http://dx.doi.org/10.1016/j.ejmech.2017.11.004] [PMID: 29133061]
[61]
Medina-O’Donnell, M.; Rivas, F.; Reyes-Zurita, F.J.; Martinez, A.; Galisteo-González, F.; Lupiañez, J.A.; Parra, A. Synthesis and in vitro antiproliferative evaluation of PEGylated triterpene acids. Fitoterapia, 2017, 120, 25-40.
[http://dx.doi.org/10.1016/j.fitote.2017.05.006] [PMID: 28552598]
[62]
Medina-O’Donnell, M.; Rivas, F.; Reyes-Zurita, F.J.; Martinez, A.; Lupiañez, J.A.; Parra, A. Diamine and PEGylated-diamine conjugates of triterpenic acids as potential anticancer agents. Eur. J. Med. Chem., 2018, 148, 325-336.
[http://dx.doi.org/10.1016/j.ejmech.2018.02.044] [PMID: 29471121]
[63]
Kahnt, M.; Loesche, A.; Serbian, I.; Hoenke, S.; Fischer, L.; Al-Harrasi, A.; Csuk, R. The cytotoxicity of oleanane derived aminocarboxamides depends on their aminoalkyl substituents. Steroids, 2019.149108422
[http://dx.doi.org/10.1016/j.steroids.2019.05.014] [PMID: 31175922]
[64]
Kumbham, S.; Paul, M.; Bhatt, H.; Ghosh, B.; Biswas, S. Oleanolic acid-conjugated poly (D, l-lactide)-based micelles for effective delivery of doxorubicin and combination chemotherapy in oral cancer. J. Mol. Liq., 2020.320114389
[http://dx.doi.org/10.1016/j.molliq.2020.114389]
[65]
Jo, H.; Oh, J.H.; Park, D.W.; Lee, C.; Min, C.K. Oleanolic acid 3-acetate, a minor element of ginsenosides, induces apoptotic cell death in ovarian carcinoma and endometrial carcinoma cells via the involvement of a reactive oxygen species-independent mitochondrial pathway. J. Ginseng Res., 2020, 44(1), 96-104.
[http://dx.doi.org/10.1016/j.jgr.2018.09.003] [PMID: 32095097]
[66]
Abdelmageed, N.; Morad, S.A.F.; Elghoneimy, A.A.; Syrovets, T.; Simmet, T.; El-Zorba, H.; El-Banna, H.A.; Cabot, M.; Abdel-Aziz, M.I. Oleanolic acid methyl ester, a novel cytotoxic mitocan, induces cell cycle arrest and ROS-Mediated cell death in castration-resistant prostate cancer PC-3 cells. Biomed. Pharmacother., 2017, 96, 417-425.
[http://dx.doi.org/10.1016/j.biopha.2017.10.027] [PMID: 29031200]
[67]
Spivak, A.; Khalitova, R.; Nedopekina, D.; Dzhemileva, L.; Yunusbaeva, M.; Odinokov, V.; D’yakonov, V.; Dzhemilev, U. Synthesis and evaluation of anticancer activities of novel c-28 guanidine-functionalized triterpene acid derivatives. Molecules, 2018, 23(11), 3000.
[http://dx.doi.org/10.3390/molecules23113000] [PMID: 30453551]
[68]
Wang, R.; Li, Y.; Huai, X.D.; Zheng, Q.X.; Wang, W.; Li, H.J.; Huai, Q.Y. Design and preparation of derivatives of oleanolic and glycyrrhetinic acids with cytotoxic properties. Drug Des. Devel. Ther., 2018, 12, 1321-1336.
[http://dx.doi.org/10.2147/DDDT.S166051] [PMID: 29861624]
[69]
Zhu, B.; Ren, C.; Du, K.; Zhu, H.; Ai, Y.; Kang, F.; Luo, Y.; Liu, W.; Wang, L.; Xu, Y.; Jiang, X.; Zhang, Y. Olean-28,13b-olide 2 plays a role in cisplatin-mediated apoptosis and reverses cisplatin resistance in human lung cancer through multiple signaling pathways. Biochem. Pharmacol., 2019.170113642
[http://dx.doi.org/10.1016/j.bcp.2019.113642] [PMID: 31541631]
[70]
Juang, Y.P.; Lin, Y.Y.; Chan, S.H.; Chang, C.K.; Shie, J.J.; Hsieh, Y.S.Y.; Guh, J.H.; Liang, P.H. Synthesis, distribution analysis and mechanism studies of N-acyl glucosamine-bearing oleanolic saponins. Bioorg. Chem., 2020.99103835
[http://dx.doi.org/10.1016/j.bioorg.2020.103835] [PMID: 32305695]
[71]
Zhang, Y.; Li, J.; Wang, Z.; Xu, M.Z.; Zeng, Z.; Huang, J.P.; Guan, Y.Q. Natural plant-derived polygalacturonic acid-oleanolic acid assemblies as oral-delivered nanomedicine for insulin resistance treatment. Chem. Eng. J., 2020.124630
[http://dx.doi.org/10.1016/j.cej.2020.124630]
[72]
Zhong, Y.Y.; Chen, H.S.; Wu, P.P.; Zhang, B.J.; Yang, Y.; Zhu, Q.Y.; Zhang, C.G.; Zhao, S.Q. Synthesis and biological evaluation of novel oleanolic acid analogues as potential α-glucosidase inhibitors. Eur. J. Med. Chem., 2019, 164, 706-716.
[http://dx.doi.org/10.1016/j.ejmech.2018.12.046] [PMID: 30677669]
[73]
Loesche, A.; Köwitsch, A.; Lucas, S.D.; Al-Halabi, Z.; Sippl, W.; Al-Harrasi, A.; Csuk, R. Ursolic and oleanolic acid derivatives with cholinesterase inhibiting potential. Bioorg. Chem., 2019, 85, 23-32.
[http://dx.doi.org/10.1016/j.bioorg.2018.12.013] [PMID: 30599410]
[74]
Meng, L.; Su, Y.; Yang, F.; Xiao, S.; Yin, Z.; Liu, J.; Zhong, J.; Zhou, D.; Yu, F. Design, synthesis and biological evaluation of amino acids-oleanolic acid conjugates as influenza virus inhibitors. Bioorg. Med. Chem., 2019, 27(23)115147
[http://dx.doi.org/10.1016/j.bmc.2019.115147] [PMID: 31635892]
[75]
Su, Y.; Meng, L.; Sun, J.; Li, W.; Shao, L.; Chen, K.; Zhou, D.; Yang, F.; Yu, F. Design, synthesis of oleanolic acid-saccharide conjugates using click chemistry methodology and study of their anti-influenza activity. Eur. J. Med. Chem., 2019.182111622
[http://dx.doi.org/10.1016/j.ejmech.2019.111622] [PMID: 31425909]
[76]
Zhang, Y.C.; Shen, Q.; Zhu, M.W.; Wang, J.; Du, Y.; Wu, J.; Li, J.X. Modified Quinoxaline-Fused Oleanolic Acid Derivatives as Inhibitors of Osteoclastogenesis and Potential Agent in Anti-Osteoporosis. ChemistrySelect, 2020, 5(4), 1526-1533.
[http://dx.doi.org/10.1002/slct.201904521]
[77]
Cui, W.; Liu, C.X.; Wang, J.; Zhang, Y.C.; Shen, Q.; Feng, Z.H.; Wu, J.; Li, J.X. An oleanolic acid derivative reduces denervation-induced muscle atrophy via activation of CNTF-mediated JAK2/STAT3 signaling pathway. Eur. J. Pharmacol., 2019.861172612
[http://dx.doi.org/10.1016/j.ejphar.2019.172612] [PMID: 31421088]
[78]
Cui, W.; Liu, C.X.; Zhang, Y.C.; Shen, Q.; Feng, Z.H.; Wang, J.; Lu, S.F.; Wu, J.; Li, J.X. A novel oleanolic acid derivative HA-19 ameliorates muscle atrophy via promoting protein synthesis and preventing protein degradation. Toxicol. Appl. Pharmacol., 2019.378114625
[http://dx.doi.org/10.1016/j.taap.2019.114625] [PMID: 31201822]
[79]
Nakamura, R.; Shirahata, T.; Konishi, N.; Takanezawa, Y.; Sone, Y.; Uraguchi, S.; Kobayashi, Y.; Kiyono, M. Oleanolic acid 3-glucoside, a synthetic oleanane-type saponin, alleviates methylmercury toxicity in vitro and in vivo. Toxicol., 2019, 417, 15-22.
[http://dx.doi.org/10.1016/j.tox.2019.02.006] [PMID: 30776458]
[80]
Spivak, A.Y.; Khalitova, R.R.; Nedopekina, D.A.; Gubaidullin, R.R. Antimicrobial properties of amine- and guanidine-functionalized derivatives of betulinic, ursolic and oleanolic acids: Synthesis and structure/activity evaluation. Steroids, 2020.154108530
[http://dx.doi.org/10.1016/j.steroids.2019.108530] [PMID: 31678136]
[81]
Yang, Y.; He, H.J.; Chang, H.; Yu, Y.; Yang, M.B.; He, Y.; Fan, Z.C.; Iyer, S.S.; Yu, P. Multivalent oleanolic acid human serum albumin conjugate as nonglycosylated neomucin for influenza virus capture and entry inhibition. Eur. J. Med. Chem., 2018, 143, 1723-1731.
[http://dx.doi.org/10.1016/j.ejmech.2017.10.070] [PMID: 29146135]
[82]
Medina-O’Donnell, M.; Rivas, F.; Reyes-Zurita, F.J.; Cano-Muñoz, M.; Martinez, A.; Lupiañez, J.A.; Parra, A. Oleanolic Acid Derivatives as Potential Inhibitors of HIV-1 Protease. J. Nat. Prod., 2019, 82(10), 2886-2896.
[http://dx.doi.org/10.1021/acs.jnatprod.9b00649] [PMID: 31617361]
[83]
Liu, L.; Li, H.; Hu, K.; Xu, Q.; Wen, X.; Cheng, K.; Chen, C.; Yuan, H.; Dai, L.; Sun, H. Synthesis and anti-inflammatory activity of saponin derivatives of δ-oleanolic acid. Eur. J. Med. Chem., 2021.209112932
[http://dx.doi.org/10.1016/j.ejmech.2020.112932] [PMID: 33131725]
[84]
Kiran, Z.; Hassan, N.; Ayub, A.; Sara, S.; Bano, Z.; Begum, S.; Siddiqui, B.S.; Fayyaz, S.; Iqbal, E. Nematicidal activity of oleanolic acid derivatives on Meloidogyne incognita. Nat. Prod. Res., 2020, 1-7.
[http://dx.doi.org/10.1080/14786419.2020.1786826] [PMID: 32696664]
[85]
Chu, F.; Zhang, W.; Guo, W.; Wang, Z.; Yang, Y.; Zhang, X.; Fang, K.; Yan, M.; Wang, P.; Lei, H. Oleanolic acid-amino acids derivatives: Design, synthesis and hepatoprotective evaluation in vitro and in vivo. Molecules, 2018, 23(2), 322.
[http://dx.doi.org/10.3390/molecules23020322] [PMID: 29393898]
[86]
Wu, P.; He, H.; Ma, H.; Tu, B.; Li, J.; Guo, S.; Chen, S.; Cao, N.; Zheng, W.; Tang, X.; Li, D.; Xu, X.; Zheng, X.; Sheng, Z.; David Hong, W.; Zhang, K. Oleanolic acid indole derivatives as novel α-glucosidase inhibitors: Synthesis, biological evaluation, and mechanistic analysis. Bioorg. Chem., 2021.107104580
[http://dx.doi.org/10.1016/j.bioorg.2020.104580] [PMID: 33418317]
[87]
Feng, A.; Yang, S.; Sun, Y.; Zhang, L.; Bo, F.; Li, L. Development and Evaluation of Oleanolic Acid Dosage Forms and Its Derivatives. BioMed Res. Int., 2020.20201308749
[http://dx.doi.org/10.1155/2020/1308749] [PMID: 33299854]
[88]
Fan, R.; Wang, H.; Zhang, L.; Ma, T.; Tian, Y.; Li, H. Nanocrystallized Oleanolic Acid Better Inhibits Proliferation, Migration and Invasion in Intracranial Glioma via Caspase-3 Pathway. J. Cancer, 2020, 11(7), 1949-1958.
[http://dx.doi.org/10.7150/jca.38847] [PMID: 32194806]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy