Indole Alkaloids with Potential Anticancer Activity

Author(s): Dan Xu, Zhi Xu*

Journal Name: Current Topics in Medicinal Chemistry

Volume 20 , Issue 21 , 2020

DOI : 10.2174/1568026620666200622150325

  Journal Home
Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Indole alkaloids, which are abundant in nature, are a significant source of pharmacologically active compounds. Indole alkaloids have the potential to exert anticancer activity via various antiproliferative mechanisms, and some of them, such as Vinblastine and Vincristinem, have already used in clinics or under clinical evaluations for the treatment of cancers. Therefore, indole alkaloids occupy an important position in the discovery of novel anticancer agents. This review emphasizes the recent development of indole alkaloids as potential anticancer agents, their structure-activity relationship, and mechanisms of action covering the articles published from 2015 to 2020.

Keywords: Indole alkaloids, Anticancer, Structure-activity relationship, Mechanisms of action, Vinblastine, Vincristine.

[1]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2020. CA Cancer J. Clin., 2020, 70(1), 7-30.
[http://dx.doi.org/10.3322/caac.21590] [PMID: 31912902]
[2]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2019. CA Cancer J. Clin., 2019, 69(1), 7-34.
[http://dx.doi.org/10.3322/caac.21551] [PMID: 30620402]
[3]
American Association for Cancer Research. Cancer progress report , 2019. Available from: . http://www.cancerprogressreport.org/2019.
[4]
International Agency for Research on Cancer. Latest global cancer data: Cancer burden rises to 18.1 million new cases and 9.6 million cancer deaths in 2019.Available from: . https://www.iarc.fr/featurednews/latest-global-cancer-data-cancer-burden-rises-to-18-1-millionnew-cases-and-9-6-million-cancer-deaths-in-2018/
[5]
Dallavalle, S.; Dobričić, V.; Lazzarato, L.; Gazzano, E.; Machuqueiro, M.; Pajeva, I.; Tsakovska, I.; Zidar, N.; Fruttero, R. Improvement of conventional anti-cancer drugs as new tools against multidrug resistant tumors. Drug Resist. Updat., 2020, 50100682
[http://dx.doi.org/10.1016/j.drup.2020.100682] [PMID: 32087558]
[6]
Efferth, T.; Saeed, M.E.M.; Kadioglu, O.; Seo, E.J.; Shirooie, S.; Mbaveng, A.T.; Nabavi, S.M.; Kuete, V. Collateral sensitivity of natural products in drug-resistant cancer cells. Biotechnol. Adv., 2020, 38107342
[http://dx.doi.org/10.1016/j.biotechadv.2019.01.009] [PMID: 30708024]
[7]
Thawabteh, A.; Juma, S.; Bader, M.; Karaman, D.; Scrano, L.; Bufo, S.A.; Karaman, R. The biological activity of natural alkaloids against herbivores, cancerous cells and pathogens. Toxins (Basel), 2019, 11(11)e656
[http://dx.doi.org/10.3390/toxins11110656] [PMID: 31717922]
[8]
Mondal, A.; Gandhi, A.; Fimognari, C.; Atanasov, A.G.; Bishayee, A. Alkaloids for cancer prevention and therapy: Current progress and future perspectives. Eur. J. Pharmacol., 2019, 858172472
[http://dx.doi.org/10.1016/j.ejphar.2019.172472] [PMID: 31228447]
[9]
Singh, T.P.; Singh, O.M. Recent progress in biological activities of indole and indole alkaloids. Mini Rev. Med. Chem., 2018, 18(1), 9-25.
[PMID: 28782480]
[10]
Sang, Y.L.; Zhang, W.M.; Lv, P.C.; Zhu, H.L. Indole-based, antiproliferative agents targeting tubulin polymerization. Curr. Top. Med. Chem., 2017, 17(2), 120-137.
[http://dx.doi.org/10.2174/1568026616666160530154812] [PMID: 27237326]
[11]
Gessica, M.; Kumar, K. The natural and synthetic indole weaponry against bacteria. Tetrahedron Lett., 2018, 59(34), 3223-3233.
[http://dx.doi.org/10.1016/j.tetlet.2018.07.045]
[12]
Qin, H.L.; Liu, J.; Fang, W.Y.; Ravindar, L.; Rakesh, K.P. Indole-based derivatives as potential antibacterial activity against methicillin-resistance Staphylococcus aureus (MRSA). Eur. J. Med. Chem., 2020, 194112245
[http://dx.doi.org/10.1016/j.ejmech.2020.112245] [PMID: 32220687]
[13]
Frederich, M.; Tits, M.; Angenot, L. Potential antimalarial activity of indole alkaloids. Trans. R. Soc. Trop. Med. Hyg., 2008, 102(1), 11-19.
[http://dx.doi.org/10.1016/j.trstmh.2007.10.002] [PMID: 18035385]
[14]
Gul, W.; Hamann, M.T. Indole alkaloid marine natural products: an established source of cancer drug leads with considerable promise for the control of parasitic, neurological and other diseases. Life Sci., 2005, 78(5), 442-453.
[http://dx.doi.org/10.1016/j.lfs.2005.09.007] [PMID: 16236327]
[15]
Bolous, M.; Arumugam, N.; Almansour, A.I.; Suresh Kumar, R.; Maruoka, K.; Antharam, V.C.; Thangamani, S. Broad-spectrum antifungal activity of spirooxindolo-pyrrolidine tethered indole/imidazole hybrid heterocycles against fungal pathogens. Bioorg. Med. Chem. Lett., 2019, 29(16), 2059-2063.
[http://dx.doi.org/10.1016/j.bmcl.2019.07.022] [PMID: 31320146]
[16]
Kumari, A.; Singh, R.K. Medicinal chemistry of indole derivatives: Current to future therapeutic prospectives. Bioorg. Chem., 2019, 89103021
[http://dx.doi.org/10.1016/j.bioorg.2019.103021] [PMID: 31176854]
[17]
Meng, L.; Guo, Q.; Liu, Y.; Chen, M.; Li, Y.; Jiang, J.; Shi, J. Indole alkaloid sulfonic acids from an aqueous extract of Isatis indigotica roots and their antiviral activity. Acta Pharm. Sin. B, 2017, 7(3), 334-341.
[http://dx.doi.org/10.1016/j.apsb.2017.04.003] [PMID: 28540170]
[18]
Chadha, N.; Silakari, O. Indoles as therapeutics of interest in medicinal chemistry: Bird’s eye view. Eur. J. Med. Chem., 2017, 134, 159-184.
[http://dx.doi.org/10.1016/j.ejmech.2017.04.003] [PMID: 28412530]
[19]
Wan, Y.; Li, Y.; Yan, C.; Yan, M.; Tang, Z. Indole: A privileged scaffold for the design of anti-cancer agents. Eur. J. Med. Chem., 2019, 183111691
[http://dx.doi.org/10.1016/j.ejmech.2019.111691] [PMID: 31536895]
[20]
Kaur, P.; Sharma, V. Prospective plant based anticancer lead molecules. Curr. Top. Med. Chem., 2018, 18(30), 2567-2583.
[http://dx.doi.org/10.2174/1568026619666181224101132] [PMID: 30582476]
[21]
Dadashpour, S.; Emami, S. Indole in the target-based design of anticancer agents: A versatile scaffold with diverse mechanisms. Eur. J. Med. Chem., 2018, 150, 9-29.
[http://dx.doi.org/10.1016/j.ejmech.2018.02.065] [PMID: 29505935]
[22]
Kaur, K.; Jaitak, V. Recent development in indole derivatives as anticancer agents for breast cancer. Anticancer. Agents Med. Chem., 2019, 19(8), 962-983.
[http://dx.doi.org/10.2174/1871520619666190312125602] [PMID: 30864529]
[23]
Gobbi, P.G.; Federico, M. What has happened to VBM (vinblastine, bleomycin, and methotrexate) chemotherapy for early-stage Hodgkin lymphoma? Crit. Rev. Oncol. Hematol., 2012, 82(1), 18-24.
[http://dx.doi.org/10.1016/j.critrevonc.2011.04.003] [PMID: 21592816]
[24]
van de Velde, M.E.; Kaspers, G.L.; Abbink, F.C.H.; Wilhelm, A.J.; Ket, J.C.F.; van den Berg, M.H. Vincristine-induced peripheral neuropathy in children with cancer: A systematic review. Crit. Rev. Oncol. Hematol., 2017, 114, 114-130.
[http://dx.doi.org/10.1016/j.critrevonc.2017.04.004] [PMID: 28477739]
[25]
Chen, A.H.; Liu, Q.L.; Ma, Y.L.; Jiang, Z.H.; Tang, J.Y.; Liu, Y.P.; Chen, G.Y.; Fu, Y.H.; Xu, W. A new monoterpenoid indole alkaloid from Ochrosia elliptica. Nat. Prod. Res., 2017, 31(13), 1490-1494.
[http://dx.doi.org/10.1080/14786419.2016.1277349] [PMID: 28068850]
[26]
Rosales, P.F.; Gower, A.; Benitez, M.L.R.; Pacheco, B.S.; Segatto, N.V.; Roesch-Ely, M.; Collares, T.; Seixas, F.K.; Moura, S. Extraction, isolation and in vitro evaluation of afnisine from Tabernaemontana catharinensis in human melanoma cells. Bioorg. Chem., 2019, 90e103079
[http://dx.doi.org/10.1016/j.bioorg.2019.103079]
[27]
Liu, V.P.; Chen, A.H.; Li, R.H.; Yang, H.W.; Bao, H.N.; Lai, L.; Zong, K.; Fu, V.H. Ochroborbone, a new cytotoxic indole alkaloid from Ochrosia borbonica. Nat. Prod. Commun., 2017, 12(4), 491-493.
[http://dx.doi.org/10.1177/1934578X1701200407] [PMID: 30520579]
[28]
Liu, Q.; Chen, A.; Jiang, Z.; Ma, Y.; Tang, J.; Wu, W.; Liu, Y.; Fu, Y. A new indole alkaloid from the stems and leaves of Nauclea officinalis. Youji Huaxue, 2018, 38, 1833-1836.
[http://dx.doi.org/10.6023/cjoc201801042]
[29]
Gao, Y.; Yu, A.L.; Li, G.T.; Hai, P.; Li, Y.; Liu, J.K.; Wang, F. Hexacyclic monoterpenoid indole alkaloids from Rauvolfia verticillata. Fitoterapia, 2015, 107, 44-48.
[http://dx.doi.org/10.1016/j.fitote.2015.10.004] [PMID: 26474672]
[30]
Shi, C.S.; Li, J.M.; Chin, C.C.; Kuo, Y.H.; Lee, Y.R.; Huang, Y.C. Evodiamine induces cell growth arrest, apoptosis and suppresses tumorigenesis in human urothelial cell carcinoma cells. Anticancer Res., 2017, 37(3), 1149-1159.
[http://dx.doi.org/10.21873/anticanres.11428] [PMID: 28314276]
[31]
Abdelfatah, S.A.A.; Efferth, T. Cytotoxicity of the indole alkaloid reserpine from Rauwolfia serpentina against drug-resistant tumor cells. Phytomedicine, 2015, 22(2), 308-318.
[http://dx.doi.org/10.1016/j.phymed.2015.01.002] [PMID: 25765838]
[32]
Wang, H.Y.; Wang, R.X.; Zhao, Y.X.; Liu, K.; Wang, F.L.; Sun, J.Y. Three new isomeric indole alkoloids from Nauclea officinalis. Chem. Biodivers., 2015, 12(8), 1256-1262.
[http://dx.doi.org/10.1002/cbdv.201400289] [PMID: 26265577]
[33]
Ivanets, E.V.; Yurchenko, A.N.; Smetanina, O.F.; Rasin, A.B.; Zhuravleva, O.I.; Pivkin, M.V.; Popov, R.S.; von Amsberg, G.; Afiyatullov, S.S.; Dyshlovoy, S.A. Asperindoles A-D and a p-terphenyl derivative from the sscidian-derived fungus Aspergillus sp. KMM 4676. Mar. Drugs, 2018, 16(7)e232
[http://dx.doi.org/10.3390/md16070232] [PMID: 29987238]
[34]
Zhang, G.J.; Hu, F.; Jiang, H.; Dai, L.M.; Liao, H.B.; Li, N.; Wang, H.S.; Pan, Y.M.; Liang, D. Mappianines A-E, structurally diverse monoterpenoid indole alkaloids from Mappianthus iodoides. Phytochemistry, 2018, 145, 68-76.
[http://dx.doi.org/10.1016/j.phytochem.2017.10.009] [PMID: 29101786]
[35]
Wang, B.; Dai, Z.; Yang, X.W.; Liu, Y.P.; Khan, A.; Yang, Z.F.; Huang, W.Y.; Wang, X.H.; Zhao, X.D.; Luo, X.D. Novel nor-monoterpenoid indole alkaloids inhibiting glioma stem cells from fruits of Alstonia scholaris. Phytomedicine, 2018, 48, 170-178.
[http://dx.doi.org/10.1016/j.phymed.2018.04.057] [PMID: 30195875]
[36]
Paluka, J.; Kanokmedhakul, K.; Soytong, M.; Soytong, K.; Yahuafai, J.; Siripong, P.; Kanokmedhakul, S. Meroterpenoid pyrones, alkaloid and bicyclic brasiliamide from the fungus Neosartorya hiratsukae. Fitoterapia, 2020, 142104485
[http://dx.doi.org/10.1016/j.fitote.2020.104485] [PMID: 31982554]
[37]
Cai, Y.S.; Sarotti, A.M.; Zhou, T.L.; Huang, R.; Qiu, G.; Tian, C.; Miao, Z.H.; Mándi, A.; Kurtán, T.; Cao, S.; Yang, S.P. Flabellipparicine, a flabelliformide-apparicine-type bisindole alkaloid from Tabernaemontana divaricate. J. Nat. Prod., 2018, 81(9), 1976-1983.
[http://dx.doi.org/10.1021/acs.jnatprod.8b00191] [PMID: 30169038]
[38]
Amna, U.H.; Tan, S.P.; Awang, K.; Ali, A.M.; Nafiah, M.A.; Ahmad, K. In vitro cytotoxic effect of indole alkaloids from the roots of Kopsia singapurensis Ridl. against the human promyelocytic leukemia (HL-60) and the human cervical cancer (HeLa) cells. Int. J. Pharm. Sci. Rev. Res., 2015, 31(2), 89-95.
[39]
Li, C.J.; Chen, S.; Sun, C.; Zhang, L.; Shi, X.; Wu, S.J. Cytotoxic monoterpenoid indole alkaloids from Alstonia yunnanensis Diels. Fitoterapia, 2017, 117, 79-83.
[http://dx.doi.org/10.1016/j.fitote.2016.12.011] [PMID: 28040532]
[40]
Mady, M.S.; Mohyeldin, M.M.; Ebrahim, H.Y.; Elsayed, H.E.; Houssen, W.E.; Haggag, E.G.; Soliman, R.F.; El Sayed, K.A. The indole alkaloid meleagrin, from the olive tree endophytic fungus Penicillium chrysogenum, as a novel lead for the control of c-Met-dependent breast cancer proliferation, migration and invasion. Bioorg. Med. Chem., 2016, 24(2), 113-122.
[http://dx.doi.org/10.1016/j.bmc.2015.11.038] [PMID: 26692349]
[41]
Wang, L.; Wang, J.F.; Mao, X.; Jiao, L.; Wang, X.J. Gelsedine-type oxindole alkaloids from Gelsemium elegans and the evaluation of their cytotoxic activity. Fitoterapia, 2017, 120, 131-135.
[http://dx.doi.org/10.1016/j.fitote.2017.06.005] [PMID: 28596027]
[42]
Chi, W.Q.; Jiang, Y.H.; Hu, J.; Pan, J. Cytotoxic and antibacterial aspidofractinine alkaloids from Kopsia hainanensis. Fitoterapia, 2018, 130, 259-264.
[http://dx.doi.org/10.1016/j.fitote.2018.09.013] [PMID: 30243778]
[43]
Long, S.Y.; Li, C.L.; Hu, J.; Zhao, Q.J.; Chen, D. Indole alkaloids from the aerial parts of Kopsia fruticosa and their cytotoxic, antimicrobial and antifungal activities. Fitoterapia, 2018, 129, 145-149.
[http://dx.doi.org/10.1016/j.fitote.2018.06.017] [PMID: 29935259]
[44]
He, J.; Zhang, F.L.; Li, Z.H.; Yang, H.X.; Shao, Q.; Feng, T.; Liu, J.K. Monoterpenoid indole alkaloids from the bark of Melodinus henryi. Fitoterapia, 2019, 138104354
[http://dx.doi.org/10.1016/j.fitote.2019.104354] [PMID: 31473334]
[45]
Shao, Q.; Ma, R.; Wu, X.; Zhang, F.L.; Li, Z.H.; Feng, T.; He, J.; Liu, J.K. Monoterpenoid indole alkaloids from the fruits of Melodinus henryi. Phytochem. Lett., 2020, 35, 53-57.
[http://dx.doi.org/10.1016/j.phytol.2019.11.003]
[46]
Novello, C.R.; Marques, L.C.; Pires, M.E.; Kutschenco, A.P.; Nakamura, C.V.; Nocchi, S.; Sarragiotto, M.H.; Mello, J.C.P. Bioactive indole alkaloids from Croton echioides. J. Braz. Chem. Soc., 2016, 27(12), 2203-2209.
[http://dx.doi.org/10.5935/0103-5053.20160112]
[47]
Zhao, N.; Li, Z.L.; Li, D.H.; Sun, Y.T.; Shan, D.T.; Bai, J.; Pei, Y.H.; Jing, Y.K.; Hua, H.M. Quinolone and indole alkaloids from the fruits of Euodia rutaecarpa and their cytotoxicity against two human cancer cell lines. Phytochemistry, 2015, 109, 133-139.
[http://dx.doi.org/10.1016/j.phytochem.2014.10.020] [PMID: 25457491]
[48]
Yu, J.S.; Lee, D.; Lee, S.R.; Lee, J.W.; Choi, C.I.; Jang, T.S.; Kang, K.S.; Kim, K.H. Chemical characterization of cytotoxic indole acetic acid derivative from mulberry fruit (Morus alba L.) against human cervical cancer. Bioorg. Chem., 2018, 76, 28-36.
[http://dx.doi.org/10.1016/j.bioorg.2017.10.015] [PMID: 29125970]
[49]
Hansen, K.Ø.; Andersen, J.H.; Bayer, A.; Pandey, S.K.; Lorentzen, M.; Jørgensen, K.B.; Sydnes, M.O.; Guttormsen, Y.; Baumann, M.; Koch, U.; Klebl, B.; Eickhoff, J.; Haug, B.E.; Isaksson, J.; Hansen, E.H. Kinase chemodiversity from the arctic: Design inhibitors based on breitfussins. J. Med. Chem., 2019, 62(22), 10167-10181.
[http://dx.doi.org/10.1021/acs.jmedchem.9b01006] [PMID: 31647655]
[50]
Chen, C.; Wang, J.; Liu, J.; Zhu, H.; Sun, B.; Wang, J.; Zhang, J.; Luo, Z.; Yao, G.; Xue, Y.; Zhang, Y. Armochaetoglobins A-J: Cytochalasan alkaloids from Chaetomium globosum TW1-1, a fungus derived from the terrestrial arthropod Armadillidium vulgare. J. Nat. Prod., 2015, 78(6), 1193-1201.
[http://dx.doi.org/10.1021/np500626x] [PMID: 26068802]
[51]
Al-Massarani, S.M.; El-Gamal, A.A.; Al-Said, M.S.; Abdel-Kader, M.S.; Ashour, A.E.; Kumar, A.; Abdel-Mageed, W.M.; Al-Rehaily, A.J.; Ghabbour, H.A.; Fun, H.K. Studies on the red sea sponge Haliclona sp. for its chemical and cytotoxic properties. Pharmacogn. Mag., 2016, 12(46), 114-119.
[http://dx.doi.org/10.4103/0973-1296.177906] [PMID: 27076747]
[52]
Alarif, W.M.; Al-Lihaibi, S.S.; Ghandourah, M.A.; Orif, M.I.; Basaif, S.A.; Ayyad, S.E.N. Cytotoxic scalarane-type sesterterpenes from the Saudi Red Sea sponge Hyrtios erectus. J. Asian Nat. Prod. Res., 2016, 18(6), 611-617.
[http://dx.doi.org/10.1080/10286020.2015.1115019] [PMID: 26630474]
[53]
Lim, J.L.; Sim, K.S.; Yong, K.T.; Loong, B.J.; Ting, K.N.; Lim, S.H.; Low, Y.Y.; Kam, T.S. Biologically active vallesamine, strychnan, and rhazinilam alkaloids from Alstonia: Pneumatophorine, a nor-secovallesamine with unusual incorporation of a 3-ethylpyridine moiety. Phytochemistry, 2015, 117, 317-324.
[http://dx.doi.org/10.1016/j.phytochem.2015.06.024] [PMID: 26125941]
[54]
Zhang, N.; Jin, W.F.; Sun, Y.P.; Wang, G.; Yu, Y.; Zhou, Z.Y.; Wang, G.K.; Liu, J.S. Indole and flavonoid from the herbs of Kalimeris shimadai. Phytochem. Lett., 2018, 28, 135-138.
[http://dx.doi.org/10.1016/j.phytol.2018.10.002]
[55]
Macedo Pereira, G.; Moreira, L.G.L.; Neto, T.D.S.N.; Moreira de Almeida, W.A.; Almeida-Lima, J.; Rocha, H.A.O.; Barbosa, E.G.; Zuanazzi, J.A.S.; de Almeida, M.V.; Grazul, R.M.; Navarro-Vázquez, A.; Hallwass, F.; Ferreira, L.S.; Fernandes-Pedrosa, M.F.; Giordani, R.B. Isolation, spectral characterization, molecular docking, and cytotoxic activity of alkaloids from Erythroxylum pungens O. E. Shulz. Phytochemistry, 2018, 155, 12-18.
[http://dx.doi.org/10.1016/j.phytochem.2018.07.003] [PMID: 30056276]
[56]
Xu, J.; Hu, Y.W.; Qu, W.; Chen, M.H.; Zhou, L.S.; Bi, Q.R.; Luo, J.G.; Liu, W.Y.; Feng, F.; Zhang, J. Cytotoxic and neuroprotective activities of constituents from Alternaria alternate, a fungal endophyte of Psidium littorale. Bioorg. Chem., 2019, 90103046
[http://dx.doi.org/10.1016/j.bioorg.2019.103046] [PMID: 31212182]
[57]
Gao, Y.; Zhou, D.S.; Hai, P.; Li, Y.; Wang, F. Hybrid monoterpenoid indole alkaloids obtained as artifacts from Rauvolfia tetraphylla. Nat. Prod. Bioprospect., 2015, 5(5), 247-253.
[http://dx.doi.org/10.1007/s13659-015-0074-2] [PMID: 26416155]
[58]
Paterna, A.; Borralho, P.M.; Gomes, S.E.; Mulhovo, S.; Rodrigues, C.M.P.; Ferreira, M.J.U. Monoterpene indole alkaloid hydrazone derivatives with apoptosis inducing activity in human HCT116 colon and HepG2 liver carcinoma cells. Bioorg. Med. Chem. Lett., 2015, 25(17), 3556-3559.
[http://dx.doi.org/10.1016/j.bmcl.2015.06.084] [PMID: 26169128]
[59]
Zhu, H.; Chen, C.; Wang, J.; Li, X.N.; Wei, G.; Guo, Y.; Yao, G.; Luo, Z.; Zhang, J.; Xue, Y.; Zhang, Y. Penicamedine A, a highly oxygenated hexacyclic indole alkaloid from Penicillium camemberti. Chem. Biodivers., 2015, 12(10), 1547-1553.
[http://dx.doi.org/10.1002/cbdv.201400412] [PMID: 26460559]
[60]
Zhang, Z.J.; Du, R.N.; He, J.; Wu, X.D.; Li, Y.; Li, R.T.; Zhao, Q.S. Vinmajorines C-E, monoterpenoid indole alkaloids from Vinca major. Helv. Chim. Acta, 2016, 99, 157-160.
[http://dx.doi.org/10.1002/hlca.201500211]
[61]
Kuok, C.F.; Zhang, J.; Fan, C.L.; Zhang, Q.W.; Fan, R.Z.; Zhang, D.M.; Zhang, X.Q.; Ye, W.C. Meloslines A and B, two novel indole alkaloids from Alstonia scholaris. Tetrahedron Lett., 2017, 58, 2740-2742.
[http://dx.doi.org/10.1016/j.tetlet.2017.05.094]
[62]
Paterna, A.; Kincses, A.; Spengler, G.; Mulhovo, S.; Molnár, J.; Ferreira, M.U. Dregamine and tabernaemontanine derivatives as ABCB1 modulators on resistant cancer cells. Eur. J. Med. Chem., 2017, 128, 247-257.
[http://dx.doi.org/10.1016/j.ejmech.2017.01.044] [PMID: 28189906]
[63]
Zhong, X.H.; Bao, M.F.; Zeng, C.X.; Zhang, B.J.; Wu, J.; Zhang, Y.; Cai, X.H. Polycyclic monoterpenoid indole alkaloids from Alstonia rostrata and their reticulate derivation. Phytochem. Lett., 2017, 20, 77-83.
[http://dx.doi.org/10.1016/j.phytol.2017.04.008]
[64]
Afiyatullov, S.S.; Zhuravleva, O.I.; Antonov, A.S.; Berdyshev, D.V.; Pivkin, M.V.; Denisenko, V.A.; Popov, R.S.; Gerasimenko, A.V.; von Amsberg, G.; Dyshlovoy, S.A.; Leshchenko, E.V.; Yurchenko, A.N. Prenylated indole alkaloids from co-culture of marine-derived fungi Aspergillus sulphureus and Isaria felina. J. Antibiot. (Tokyo), 2018, 71(10), 846-853.
[http://dx.doi.org/10.1038/s41429-018-0072-9] [PMID: 29884864]
[65]
Wei, J.J.; Wang, W.Q.; Song, W.B.; Li, J.; Xuan, L.J. Three new indole alkaloids from Mappianthus iodoides. Phytochem. Lett., 2018, 23, 1-4.
[http://dx.doi.org/10.1016/j.phytol.2017.10.018]
[66]
Yuan, Y.X.; Guo, F.; He, H.P.; Zhang, Y.; Hao, X.J. Two new monoterpenoid indole alkaloids from Alstonia rostrata. Nat. Prod. Res., 2018, 32(7), 844-848.
[http://dx.doi.org/10.1080/14786419.2017.1360886] [PMID: 28768429]
[67]
Feng, W.S.; Guo, M.H.; Yin, Y.G.; Cao, Y.G.; Yang, C.L.; Wang, Y.Y.; Qi, M.; Zhang, Y.L.; Ren, Y.J.; Liu, Y.L.; Zheng, X.K. A new indole alkaloid from bulbils of Dioscorea opposite Thunb. Yao Xue Xue Bao, 2018, 53(7), 1131-1133.
[68]
Yu, Z.P.; Wang, Y.Y.; Yu, S.J.; Bao, J.; Yu, J.H.; Zhang, H. Absolute structure assignment of an iridoid-monoterpenoid indole alkaloid hybrid from Dipsacus asper. Fitoterapia, 2019, 135, 99-106.
[http://dx.doi.org/10.1016/j.fitote.2019.04.015] [PMID: 31051193]
[69]
Krishnan, P.; Mai, C.W.; Yong, K.T.; Low, Y.Y.; Lim, K.H. Alstobrogaline, an unusual pentacyclic monoterpenoid indole alkaloid with aldimine and aldimine-N-oxide moieties from Alstonia scholaris. Tetrahedron Lett., 2019, 60, 789-791.
[http://dx.doi.org/10.1016/j.tetlet.2019.02.018]
[70]
Huo, Z.Q.; Zhao, Q.; Liu, J.W.; Zhu, W.T.; Hao, X.J.; Zhang, Y. Bousangine A, a novel C-17-nor aspidosperma-type monoterpenoid indole alkaloid from Bousigonia angustifolia. Fitoterapia, 2020, 142104491
[http://dx.doi.org/10.1016/j.fitote.2020.104491] [PMID: 32032634]
[71]
Zhang, T.; Ma, C.J.; Wei, Y.L.; Si, J.G.; Fu, L.; Dong, J.X.; Zou, Z.M. The novel indole glucoalkaloid and secoiridoid glucoside from Tripterospermum chinense. Phytochem. Lett., 2020, 35, 191-196.
[http://dx.doi.org/10.1016/j.phytol.2019.12.005]
[72]
Zhang, Z.J.; Du, R.N.; He, J.; Wu, X.D.; Li, Y.; Li, R.T.; Zhao, Q.S. Three new monoterpenoid indole alkaloids from Vinca major. J. Asian Nat. Prod. Res., 2016, 18(4), 328-333.
[http://dx.doi.org/10.1080/10286020.2015.1094463] [PMID: 26700398]
[73]
Zhang, B.J.; Liu, C.; Bao, M.F.; Zhong, X.H.; Ni, L.; Wu, J.; Cai, X.H. Novel monoterpenoid indole alkaloids from Melodinus yunnanensis. Tetrahedron, 2017, 73, 5821-5826.
[http://dx.doi.org/10.1016/j.tet.2017.08.008]
[74]
Yang, W.X.; Chen, Y.F.; Yang, J.; Huang, T.; Wu, L.L.; Xiao, N.; Hao, X.J.; Zhang, Y.H. Monoterpenoid indole alkaloids from Gardneria multiflora. Fitoterapia, 2018, 124, 8-11.
[http://dx.doi.org/10.1016/j.fitote.2017.09.017] [PMID: 29128600]
[75]
Rahman, M.T.; Tiruveedhula, V.V.N.P.B.; Cook, J.M. Synthesis of bisindole alkaloids from the Apocynaceae which contain a macroline or sarpagine unit: A review. Molecules, 2016, 21(11)e1525
[http://dx.doi.org/10.3390/molecules21111525] [PMID: 27854259]
[76]
Qian, S.; Guo, R.; Dong, D.; Bao, B.; Wang, S.; Wu, W. Biosynthetic pathways and bioactivities of bisindole compounds: A short review. Med. Res., 2017, 1, 20-24.
[77]
Gaboriaud-Kolar, N.; Vougogiannopoulou, K.; Skaltsounis, A.L. Indirubin derivatives: a patent review (2010 - present). Expert Opin. Ther. Pat., 2015, 25(5), 583-593.
[http://dx.doi.org/10.1517/13543776.2015.1019865] [PMID: 25887337]
[78]
Zhang, Y.Z.; Du, H.Z.; Liu, H.L.; He, Q.S.; Xu, Z. Isatin dimers and their biological activities. Arch. Pharm. (Weinheim), 2020, 353(3)e1900299
[http://dx.doi.org/10.1002/ardp.201900299] [PMID: 31985855]
[79]
Banerjee, S.; Kong, D.; Wang, Z.; Bao, B.; Hillman, G.G.; Sarkar, F.H. Attenuation of multi-targeted proliferation-linked signaling by 3,3′-diindolylmethane (DIM): from bench to clinic. Mutat. Res., 2011, 728(1-2), 47-66.
[http://dx.doi.org/10.1016/j.mrrev.2011.06.001] [PMID: 21703360]
[80]
Tian, X.; Liu, K.; Zu, X.; Ma, F.; Li, Z.; Lee, M.; Chen, H.; Li, Y.; Zhao, Y.; Liu, F.; Oi, N.; Bode, A.M.; Dong, Z.; Kim, D.J. 3,3′-Diindolylmethane inhibits patient-derived xenograft colon tumor growth by targeting COX1/2 and ERK1/2. Cancer Lett., 2019, 448, 20-30.
[http://dx.doi.org/10.1016/j.canlet.2019.01.031] [PMID: 30716361]
[81]
Li, W.X.; Chen, L.P.; Sun, M.Y.; Li, J.T.; Liu, H.Z.; Zhu, W. 3′3-Diindolylmethane inhibits migration, invasion and metastasis of hepatocellular carcinoma by suppressing FAK signaling. Oncotarget, 2015, 6(27), 23776-23792.
[http://dx.doi.org/10.18632/oncotarget.4196] [PMID: 26068982]
[82]
Ye, Y.; Fang, Y.; Xu, W.; Wang, Q.; Zhou, J.; Lu, R. 3,3′-Diindolylmethane induces anti-human gastric cancer cells by the miR-30e-ATG5 modulating autophagy. Biochem. Pharmacol., 2016, 115, 77-84.
[http://dx.doi.org/10.1016/j.bcp.2016.06.018] [PMID: 27372603]
[83]
Lee, B.D.; Yoo, J.M.; Baek, S.Y.; Li, F.Y.; Sok, D.E.; Kim, M.R. 3,3′-Diindolylmethane promotes BDNF and antioxidant enzyme formation via TrkB/Akt pathway activation for neuroprotection against oxidative stress-induced apoptosis in hippocampal neuronal cells. Antioxidants, 2019, 9(1)e3
[http://dx.doi.org/10.3390/antiox9010003] [PMID: 31861353]
[84]
Zhu, P.; Zhou, K.; Lu, S.; Bai, Y.; Qi, R.; Zhang, S. Modulation of aryl hydrocarbon receptor inhibits esophageal squamous cell carcinoma progression by repressing COX2/PGE2/STAT3 axis. J. Cell Commun. Signal., 2020, 14(2), 175-192.
[85]
Zołek, T.; Trzeciak, A. The mechanism of action of indole-3-carbinol and 3,3′-diindolylmethane in cancer chemoprevention. Biuletyn Wydzialu Farmaceutycznego Warszawskiego Uniwersytetu Medycznego, 2017, 2, 8-15.
[86]
Wu, T.Y.; Khor, T.O.; Su, Z.Y.; Saw, C.L.L.; Shu, L.; Cheung, K.L.; Huang, Y.; Yu, S.; Kong, A.N.T. Epigenetic modifications of Nrf2 by 3,3′-diindolylmethane in vitro in TRAMP C1 cell line and in vivo TRAMP prostate tumors. AAPS J., 2013, 15(3), 864-874.
[http://dx.doi.org/10.1208/s12248-013-9493-3] [PMID: 23658110]
[87]
Yuan, M.X.; Qiu, Y.; Ran, Y.Q.; Feng, G.K.; Deng, R.; Zhu, X.F.; Lan, W.J.; Li, H.J. Exploration of indole alkaloids from marine fungus Pseudallescheria boydii F44-1 using an amino acid-directed strategy. Mar. Drugs, 2019, 17(2)e77
[http://dx.doi.org/10.3390/md17020077] [PMID: 30678113]
[88]
Elsbaey, M.; Ahmed, K.F.M.; Elsebai, M.F.; Zaghloul, A.; Amer, M.M.A.; Lahloub, M.I. Cytotoxic constituents of Alocasia macrorrhiza. Z. Natforsch. C J. Biosci., 2017, 72(1-2), 21-25.
[http://dx.doi.org/10.1515/znc-2015-0157] [PMID: 27497869]
[89]
Wright, A.E.; Killday, K.B.; Chakrabarti, D.; Guzmán, E.A.; Harmody, D.; McCarthy, P.J.; Pitts, T.; Pomponi, S.A.; Reed, J.K.; Roberts, B.F.; Rodrigues Felix, C.; Rohde, K.H. Dragmacidin G. A bioactive bis-indole alkaloid from a deep-water sponge of the genus spongosorites. Mar. Drugs, 2017, 15(1)e16
[http://dx.doi.org/10.3390/md15010016] [PMID: 28085024]
[90]
Gubian, J.R.; Oliveira, M.C.S.; Neponuceno, R.A.R.; Camargo, M.J.; Garcez, W.S.; Biz, A.R.; Soares, M.A.; Araujo, A.R. Bolzani, V. da S.; Lisboa, H. C. F.; Sousa Jr., P. T.; Vasconcelos, L. G.; Ribeiro, T. A. N.; Oliveira, J. M.; Banzato, T. P.; Lima, C. A.; Longato, G. B.; Batista Jr., J. M.; Berlinck, R. G. S.; Teles, H. L. Cytotoxic prenylated indole alkaloid produced by the endophytic fungus Aspergillus terreus P63. Phytochem. Lett., 2019, 32, 162-167.
[91]
Yeap, J.S.Y.; Saad, H.M.; Tan, C.H.; Sim, K.S.; Lim, S.H.; Low, Y.Y.; Kam, T.S. Macroline-sarpagine bisindole alkaloids with antiproliferative activity from Alstonia penangiana. J. Nat. Prod., 2019, 82(11), 3121-3132.
[http://dx.doi.org/10.1021/acs.jnatprod.9b00712] [PMID: 31642315]
[92]
Yeap, J.S.Y.; Navanesan, S.; Sim, K.S.; Yong, K.T.; Gurusamy, S.; Lim, S.H.; Low, Y.Y.; Kam, T.S. Ajmaline, oxindole, and cytotoxic macroline-akuammiline bisindole alkaloids from Alstonia penangiana. J. Nat. Prod., 2018, 81(5), 1266-1277.
[http://dx.doi.org/10.1021/acs.jnatprod.8b00170] [PMID: 29746134]
[93]
Yap, W.S.; Gan, C.Y.; Sim, K.S.; Lim, S.H.; Low, Y.Y.; Kam, T.S. Aspidofractinine and eburnane alkaloids from a north borneo kopsia. Ring-contracted, additional ring-fused, and Paucidactin-Type aspidofractinine alkaloids from K. pauciflora. J. Nat. Prod., 2016, 79(1), 230-239.
[http://dx.doi.org/10.1021/acs.jnatprod.5b00992] [PMID: 26717050]
[94]
Sim, D.S.Y.; Navanesan, S.; Sim, K.S.; Gurusamy, S.; Lim, S.H.; Low, Y.Y.; Kam, T.S. Conolodinines A-D, aspidosperma-aspidosperma bisindole alkaloids with antiproliferative activity from Tabernaemontana corymbose. J. Nat. Prod., 2019, 82(4), 850-858.
[http://dx.doi.org/10.1021/acs.jnatprod.8b00919] [PMID: 30869890]
[95]
Liu, Y.P.; Yue, G.G.L.; Lee, J.K.M.; Feng, T.; Zhao, Y.L.; Li, Y.; Lau, C.B.; Luo, X.D. Melodinine V, an antitumor bisindole alkaloid with selective cytotoxicity from Melodinus henryi. Bioorg. Med. Chem. Lett., 2016, 26(20), 4895-4898.
[http://dx.doi.org/10.1016/j.bmcl.2016.09.023] [PMID: 27650926]
[96]
Yi, W.F.; Chen, D.Z.; Ding, X.; Li, X.N.; Li, S.L.; Di, Y.T.; Zhang, Y.; Hao, X.J. Cytotoxic indole alkaloids from Melodinus khasianus and Melodinus tenuicaudatus. Fitoterapia, 2018, 128, 162-168.
[http://dx.doi.org/10.1016/j.fitote.2018.05.015] [PMID: 29772302]
[97]
Fang, Z.Y.; Ren, Y.D.; Du, S.Y.; Zhang, M.; Wang, Y.S.; Fang, L.; Zhang, H. Melosuavine I, an apoptosis-inducing bisindole alkaloid from Melodinus suaveolens. Fitoterapia, 2019, 133, 175-179.
[http://dx.doi.org/10.1016/j.fitote.2018.12.026] [PMID: 30660654]
[98]
Shao, S.; Zhang, H.; Yuan, C.M.; Zhang, Y.; Cao, M.M.; Zhang, H.Y.; Feng, Y.; Ding, X.; Zhou, Q.; Zhao, Q.; He, H.P.; Hao, X.J. Cytotoxic indole alkaloids from the fruits of Melodinus cochinchinensis. Phytochemistry, 2015, 116, 367-373.
[http://dx.doi.org/10.1016/j.phytochem.2015.02.028] [PMID: 25817833]
[99]
Zhang, B.J.; Teng, X.F.; Bao, M.F.; Zhong, X.H.; Ni, L.; Cai, X.H. Cytotoxic indole alkaloids from Tabernaemontana officinalis. Phytochemistry, 2015, 120, 46-52.
[http://dx.doi.org/10.1016/j.phytochem.2014.12.025] [PMID: 25687604]
[100]
Lim, K.H.; Raja, V.J.; Bradshaw, T.D.; Lim, S.H.; Low, Y.Y.; Kam, T.S. Ibogan, tacaman, and cytotoxic bisindole alkaloids from tabernaemontana. Cononusine, an iboga alkaloid with unusual incorporation of a pyrrolidone moiety. J. Nat. Prod., 2015, 78(5), 1129-1138.
[http://dx.doi.org/10.1021/acs.jnatprod.5b00117] [PMID: 25919190]
[101]
Zhang, Y.; Yuan, Y.X.; Goto, M.; Guo, L.L.; Li, X.N.; Morris-Natschke, S.L.; Lee, K.H.; Hao, X.J. Taburnaemines A-I, cytotoxic Vobasinyl-Iboga-Type bisindole alkaloids from Tabernaemontana corymbose. J. Nat. Prod., 2018, 81(3), 562-571.
[http://dx.doi.org/10.1021/acs.jnatprod.7b00949] [PMID: 29319316]
[102]
Paterna, A.; Gomes, S.E.; Borralho, P.M.; Mulhovo, S.; Rodrigues, C.M.P.; Ferreira, M.U. (3'R)-hydroxytabernaelegantine C: A bisindole alkaloid with potent apoptosis inducing activity in colon (HCT116, SW620) and liver (HepG2) cancer cells. J. Ethnopharmacol., 2016, 194, 236-244.
[http://dx.doi.org/10.1016/j.jep.2016.09.020] [PMID: 27616029]
[103]
Paterna, A.; Gomes, S.E.; Borralho, P.M.; Mulhovo, S.; Rodrigues, C.M.P.; Ferreira, M.U. Vobasinyl-Iboga alkaloids from Tabernaemontana elegans: Cell cycle arrest and apoptosis-inducing activity in HCT116 colon cancer cells. J. Nat. Prod., 2016, 79(10), 2624-2634.
[http://dx.doi.org/10.1021/acs.jnatprod.6b00552] [PMID: 27704811]
[104]
Yuan, Y.X.; Zhang, Y.; Guo, L.L.; Wang, Y.H.; Goto, M.; Morris-Natschke, S.L.; Lee, K.H.; Hao, X.J. Tabercorymines A and B, two Vobasinyl-Ibogan-Type bisindole alkaloids from Tabernaemontana corymbose. Org. Lett., 2017, 19(18), 4964-4967.
[http://dx.doi.org/10.1021/acs.orglett.7b02445] [PMID: 28876071]
[105]
Zhou, S.Y.; Zhou, T.L.; Qiu, G.; Huan, X.; Miao, Z.H.; Yang, S.P.; Cao, S.; Fan, F.; Cai, Y.S. Three new cytotoxic monoterpenoid bisindole alkaloids from Tabernaemontana bufalina. Planta Med., 2018, 84(15), 1127-1133.
[http://dx.doi.org/10.1055/a-0608-4988] [PMID: 29689587]
[106]
Sim, D.S.Y.; Teoh, W.Y.; Sim, K.S.; Lim, S.H.; Thomas, N.F.; Low, Y.Y.; Kam, T.S. Vobatensines A-F, cytotoxic Iboga-Vobasine bisindoles from Tabernaemontana corymbose. J. Nat. Prod., 2016, 79(4), 1048-1055.
[http://dx.doi.org/10.1021/acs.jnatprod.5b01117] [PMID: 26918761]
[107]
Wang, X.D.; Li, C.Y.; Jiang, M.M.; Li, D.; Wen, P.; Song, X.; Chen, J.D.; Guo, L.X.; Hu, X.P.; Li, G.Q.; Zhang, J.; Wang, C.H.; He, Z.D. Induction of apoptosis in human leukemia cells through an intrinsic pathway by cathachunine, a unique alkaloid isolated from Catharanthus roseus. Phytomedicine, 2016, 23(6), 641-653.
[http://dx.doi.org/10.1016/j.phymed.2016.03.003] [PMID: 27161405]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 20
ISSUE: 21
Year: 2020
Page: [1938 - 1949]
Pages: 12
DOI: 10.2174/1568026620666200622150325
Price: $65

Article Metrics

PDF: 26
HTML: 1



Most Downloaded Article(s)