Abstract
Background: Breast Cancer (BC) is the second most common cause of cancer related deaths in women. Due to severe side effects and multidrug resistance, current therapies like hormonal therapy, surgery, radiotherapy and chemotherapy become ineffective. Also, the existing drugs for BC treatment are associated with several drawbacks such as poor oral bioavailability, non-selectivity and poor pharmacodynamics properties. Therefore, there is an urgent need for the development of more effective and safer anti BC agents.
Objective: This article explored in detail the possibilities of indole-based heterocyclic compounds as anticancer agents with breast cancer as their major target.
Methods: Recent literature related to indole derivatives endowed with encouraging anti BC potential is reviewed. With special focus on BC, this review offers a detailed account of multiple mechanisms of action of various indole derivatives: aromatase inhibitor, tubulin inhibitor, microtubule inhibitor, targeting estrogen receptor, DNA-binding mechanism, induction of apoptosis, inhibition of PI3K/AkT/NFkB/mTOR, and HDAC inhibitors, by which these derivatives have shown promising anticancer potential.
Results: Exhaustive literature survey indicated that indole derivatives are associated with properties of inducing apoptosis and disturbing tubulin assembly. Indoles are also associated with the inhibition of NFkB/mTOR/PI3K/AkT and regulation of estrogen-mediated activity. Furthermore, indole derivatives have been found to modulate critical targets such as topoisomerase and HDAC. These derivatives have shown significant activity against breast cancer cells.
Conclusion: In BC, indole derivatives seem to be quite competent and act through various mechanisms that are well established in case of BC. This review has shown that indole derivatives can further be explored for the betterment of BC chemotherapy. A lot of potential is still hidden which demands to be discovered for upgrading BC chemotherapy.
Keywords: Indole, anticancer, breast cancer, signal transduction, ER, chemotherapy.
Graphical Abstract
[1]
Malki, A.; Elbayaa, R.Y.; Ali, O.; Sultan, A.; Youssef, A.M. Novel quinuclidinone derivatives induced apoptosis in human breast cancer via targeting p53. Bioorg. Chem., 2017, 72, 57-63.
[2]
Torre, L.A.; Bray, F.; Siegel, R.L.; Ferlay, J.; Lortet‐Tieulent, J.; Jemal, A. Global cancer statistics, 2012. CA Cancer J. Clin., 2015, 65(2), 87-108.
[3]
Jabłońska-Trypuć, A.; Świderski, G.; Krętowski, R.; Lewandowski, W. Newly synthesized doxorubicin complexes with selected metals-synthesis, structure and anti-breast cancer activity. Molecules, 2017, 22(7), 1106.
[4]
Fan, L.; Cao, X.; Yan, H.; Wang, Q.; Tian, X.; Zhang, L.; He, X.; Borjihan, G. The synthetic antihyperlipidemic drug potassium piperate selectively kills breast cancer cells through inhibiting G1-S-phase transition and inducing apoptosis. Oncotarget, 2017, 8(29), 47250.
[5]
Liu, L.; Tang, Z.; Wu, C.; Li, X.; Huang, A.; Lu, X.; You, Q.; Xiang, H. Synthesis and biological evaluation of 4, 6-diaryl-2-pyrimidinamine derivatives as anti-breast cancer agents. Bioorg. Med. Chem. Lett., 2018, 28(6), 1138-1142.
[7]
Sayeed, M.A.; Bracci, M.; Lazzarini, R.; Tomasetti, M.; Amati, M.; Lucarini, G.; Di Primio, R.; Santarelli, L. Use of potential dietary phytochemicals to target miRNA: promising option for breast cancer prevention and treatment? J. Funct. Foods, 2017, 28, 177-193.
[8]
Fortes, M.P.; da Silva, P.B.; da Silva, T.G.; Kaufman, T.S.; Militao, G.C.; Silveira, C.C. Synthesis and preliminary evaluation of 3-thiocyanato-1H-indoles as potential anticancer agents. Eur. J. Med. Chem., 2016, 118, 21-26.
[9]
Singh Sidhu, J.; Singla, R.; Jaitak, V. Indole derivatives as anticancer agents for breast cancer therapy: A review. Anticancer. Agents Med. Chem., 2016, 16(2), 160-173.
[10]
Rathi, K.A.; Syed, R.; Singh, V.; Shin, H-S.; Patel, V.R. Kinase inhibitor indole derivatives as anticancer agents: A patent review. Recent Patents Anticancer Drug Discov., 2017, 12(1), 55-72.
[11]
Dadashpour, S.; Emami, S. Indole in the target-based design of anticancer agents: A versatile scaffold with diverse mechanism. Eur. J. Med. Chem., 2018, 150, 9-29.
[12]
Almutairi, M.S.; Zakaria, A.S.; Ignasius, P.P.; Al-Wabli, R.I.; Joe, I.H.; Attia, M.I. Synthesis, spectroscopic investigations, DFT studies, molecular docking and antimicrobial potential of certain new indole-isatin molecular hybrids: Experimental and theoretical approaches. J. Mol. Struct., 2018, 1153, 333-345.
[13]
Lin, W.; Zheng, Y-X.; Xun, Z.; Huang, Z-B.; Shi, D-Q. Microwave-assisted regioselective synthesis of 3-functionalized indole derivatives via three-component domino reaction. ACS Comb. Sci., 2017, 19(11), 708-713.
[14]
Abdelhamid, A.O.; Gomha, S.M.; Abdelriheem, N.A.; Kandeel, S.M. Synthesis of new 3-heteroarylindoles as potential anticancer agents. Molecules, 2016, 21(7), 929.
[15]
Bhale, P.S.; Chavan, H.V.; Dongare, S.B.; Shringare, S.N.; Mule, Y.B.; Nagane, S.S.; Bandgar, B.P. Synthesis of extended conjugated indolyl chalcones as potent anti-breast cancer, anti-inflammatory and antioxidant agents. Bioorg. Med. Chem. Lett., 2017, 27(7), 1502-1507.
[16]
Szaefer, H.; Krajka-Kuźniak, V.; Licznerska, B.; Bartoszek, A.; Baer-Dubowska, W. Cabbage juices and indoles modulate the expression profile of AhR, ERα, and Nrf2 in human breast cell lines. Nutr. Cancer, 2015, 67(8), 1344-1356.
[17]
Barigye, S.J.; Freitas, M.P.; Ausina, P.; Zancan, P.; Sola-Penna, M.; Castillo-Garit, J.A. Discrete fourier transform-based multivariate image analysis: Application to modeling of aromatase inhibitory activity. ACS Comb. Sci., 2018, 20(2), 75-81.
[18]
Yadav, M.R.; Barmade, M.A.; Tamboli, R.S.; Murumkar, P.R. Developing steroidal aromatase inhibitors-an effective armament to win the battle against breast cancer. Eur. J. Med. Chem., 2015, 105, 1-38.
[19]
Ghosh, D.; Lo, J.; Egbuta, C. Recent progress in the discovery of next generation inhibitors of aromatase from the structure-function perspective. J. Med. Chem., 2016, 59(11), 5131-5148.
[20]
Recanatini, M.; Cavalli, A. Comparative molecular field analysis of non-steroidal aromatase inhibitors: An extended model for two different structural classes. Bioorg. Med. Chem., 1998, 6(4), 377-388.
[21]
Osborne, C.K.; Schiff, R. Aromatase inhibitors: future directions. J. Steroid Biochem. Mol. Biol., 2005, 95(1-5), 183-187.
[22]
Brodie, A.; Sabnis, G.; Jelovac, D. Aromatase and breast cancer. J. Steroid Biochem. Mol. Biol., 2006, 102(1-5), 97-102.
[23]
Spinelli, G.; Tomao, F.; Miele, E.; Pasciuti, G.; Russillo, M.; Tomao, S. Aromatase inhibitors in advanced breast cancer. Recenti Prog. Med., 2008, 99(1), 34-38.
[24]
Dutta, U.; Pant, K. Aromatase inhibitors: Past, present and future in breast cancer therapy. Med. Oncol., 2008, 25(2), 113-124.
[25]
Colozza, M.; Minenza, E.; Nunzi, M.; Sabatini, S.; Dinh, P.; Califano, R.; De Azambuja, E. Aromatase inhibitors: a new reality for the adjuvant endocrine treatment of early-stage breast cancer in postmenopausal women.In: Recent Advances in Medicinal Chemistry; Elsevier, 2015, Vol. 1, pp. 99-130.
[26]
Gobbi, S.; Cavalli, A.; Bisi, A.; Recanatini, M. From nonsteroidal aromatase inhibitors to multifunctional drug candidates: Classic and innovative strategies for the treatment of breast cancer. Curr. Top. Med. Chem., 2008, 8(10), 869-887.
[27]
Neves, M.A.; Dinis, T.C.; Colombo, G.; Melo, M.L.S. An efficient steroid pharmacophore-based strategy to identify new aromatase inhibitors. Eur. J. Med. Chem., 2009, 44(10), 4121-4127.
[28]
Jha, T.; Adhikari, N.; Halder, A.K.; Saha, A. Ligand-and structure-based drug design of non-steroidal aromatase inhibitors (NSAIs) in breast cancer.In: Quantitative Structure-Activity Relationships in Drug Design, Predictive Toxicology, and Risk Assessment; IGI Global, 2015, pp. 400-470.
[29]
Adhikari, N.; Amin, S.A.; Saha, A.; Jha, T. Combating breast cancer with non-steroidal aromatase inhibitors (NSAIs): Understanding the chemico-biological interactions through comparative SAR/QSAR study. Eur. J. Med. Chem., 2017, 137, 365-438.
[30]
Ahmad, I. Recent developments in steroidal and nonsteroidal aromatase inhibitors for the chemoprevention of estrogen-dependent breast cancer. Eur. J. Med. Chem., 2015, 102, 375-386.
[31]
Neves, M.A.; Dinis, T.C.; Colombo, G.; Sá e Melo, M.L. Fast three dimensional pharmacophore virtual screening of new potent non-steroid aromatase inhibitors. J. Med. Chem., 2008, 52(1), 143-150.
[32]
Kang, H.; Xiao, X.; Huang, C.; Yuan, Y.; Tang, D.; Dai, X.; Zeng, X. Potent aromatase inhibitors and molecular mechanism of inhibitory action. Eur. J. Med. Chem., 2018, 143, 426-437.
[33]
Friesner, R.A.; Banks, J.L.; Murphy, R.B.; Halgren, T.A.; Klicic, J.J.; Mainz, D.T.; Repasky, M.P.; Knoll, E.H.; Shelley, M.; Perry, J.K. Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J. Med. Chem., 2004, 47(7), 1739-1749.
[34]
Wang, R.; Shi, H-F.; Zhao, J-F.; He, Y-P.; Zhang, H-B.; Liu, J-P. Design, synthesis and aromatase inhibitory activities of novel indole-imidazole derivatives. Bioorg. Med. Chem. Lett., 2013, 23(6), 1760-1762.
[35]
Lézé, M-P.; Palusczak, A.; Hartmann, R.W.; Le Borgne, M. Synthesis of 6-or 4-functionalized indoles via a reductive cyclization approach and evaluation as aromatase inhibitors. Bioorg. Med. Chem. Lett., 2008, 18(16), 4713-4715.
[36]
Marchand, P.; Le Borgne, M.; Palzer, M.; Le Baut, G.; Hartmann, R.W. Preparation and pharmacological profile of 7-(α-Azolylbenzyl)-1H-indoles and indolines as new aromatase inhibitors. Bioorg. Med. Chem. Lett., 2003, 13(9), 1553-1555.
[37]
Lézé, M-P.; Borgne, M.L.; Marchand, P.; Loquet, D.; Kogler, M.; Baut, G.L.; Palusczak, A.; Hartmann, R.W. 2-and 3-[(aryl)(azolyl) methyl] indoles as potential non-steroidal aromatase inhibitors. J. Enzyme Inhib. Med. Chem., 2004, 19(6), 549-557.
[38]
Lézé, M-P.; Le Borgne, M.; Pinson, P.; Palusczak, A.; Duflos, M.; Le Baut, G.; Hartmann, R.W. Synthesis and biological evaluation of 5-[(aryl)(1H-imidazol-1-yl) methyl]-1H-indoles: Potent and selective aromatase inhibitors. Bioorg. Med. Chem. Lett., 2006, 16(5), 1134-1137.
[39]
Zhou, Q.; Zhu, J.; Chen, J.; Ji, P.; Qiao, C. N-Arylsulfonylsubstituted-1H indole derivatives as small molecule dual inhibitors of signal transducer and activator of transcription 3 (STAT3) and tubulin. Bioorg. Med. Chem., 2018, 26(1), 96-106.
[40]
Yan, J.; Hu, J.; An, B.; Huang, L.; Li, X. Design, synthesis, and biological evaluation of cyclic-indole derivatives as anti-tumor agents via the inhibition of tubulin polymerization. Eur. J. Med. Chem., 2017, 125, 663-675.
[42]
Kaur, R.; Kaur, G.; Gill, R.K.; Soni, R.; Bariwal, J. Recent developments in tubulin polymerization inhibitors: An overview. Eur. J. Med. Chem., 2014, 87, 89-124.
[43]
Lu, Y.; Chen, J.; Xiao, M.; Li, W.; Miller, D.D. An overview of tubulin inhibitors that interact with the colchicine binding site. Pharm. Res., 2012, 29(11), 2943-2971.
[44]
Hu, M.J.; Zhang, B.; Yang, H.K.; Liu, Y.; Chen, Y.R.; Ma, T.Z.; Lu, L.; You, W.W.; Zhao, P.L. Design, synthesis and molecular docking studies of novel indole-pyrimidine hybrids as tubulin polymerization inhibitors. Chem. Biol. Drug Des., 2015, 86(6), 1491-1500.
[45]
Kamath, P.R.; Sunil, D.; Ajees, A.A. Synthesis of indole-quinoline-oxadiazoles: Their anticancer potential and computational tubulin binding studies. Res. Chem. Intermed., 2016, 42(6), 5899-5914.
[46]
Kim, B-H.; Yi, E.H.; Ye, S-K. Signal transducer and activator of transcription 3 as a therapeutic target for cancer and the tumor microenvironment. Arch. Pharm. Res., 2016, 39(8), 1085-1099.
[47]
Youssif, B.G.; Abdelrahman, M.H.; Abdelazeem, A.H.; Ibrahim, H.M.; Salem, O.I.; Mohamed, M.F.; Treambleau, L.; Bukhari, S.N.A. Design, synthesis, mechanistic and histopathological studies of small-molecules of novel indole-2-carboxamides and pyrazino [1, 2-a] indol-1 (2H)-ones as potential anticancer agents effecting the reactive oxygen species production. Eur. J. Med. Chem., 2018, 146, 260-273.
[48]
Wang, Y-T.; Qin, Y-J.; Yang, N.; Zhang, Y-L.; Liu, C-H.; Zhu, H-L. Synthesis, biological evaluation, and molecular docking studies of novel 1-benzene acyl-2-(1-methylindol-3-yl)-benzimidazole derivatives as potential tubulin polymerization inhibitors. Eur. J. Med. Chem., 2015, 99, 125-137.
[49]
Yan, J.; Chen, J.; Zhang, S.; Hu, J.; Huang, L.; Li, X. Synthesis, evaluation, and mechanism study of novel indole-chalcone derivatives exerting effective antitumor activity through microtubule destabilization in vitro and in vivo. J. Med. Chem., 2016, 59(11), 5264-5283.
[50]
Ramya, P.S.; Angapelly, S.; Guntuku, L.; Digwal, C.S.; Babu, B.N.; Naidu, V.; Kamal, A. Synthesis and biological evaluation of curcumin inspired indole analogues as tubulin polymerization inhibitors. Eur. J. Med. Chem., 2017, 127, 100-114.
[51]
Carbone, A.; Parrino, B.; Barraja, P.; Spanò, V.; Cirrincione, G.; Diana, P.; Maier, A.; Kelter, G.; Fiebig, H-H. Synthesis and antiproliferative activity of 2, 5-bis (3′-indolyl) pyrroles, analogues of the marine alkaloid nortopsentin. Mar. Drugs, 2013, 11(3), 643-654.
[52]
Tantak, M.P.; Klingler, L.; Arun, V.; Kumar, A.; Sadana, R.; Kumar, D. Design and synthesis of bis (indolyl) ketohydrazide-hydrazones: Identification of potent and selective novel tubulin inhibitors. Eur. J. Med. Chem., 2017, 136, 184-194.
[53]
Le Grand, A.; André-Leroux, G.L.; Marteil, G.L.; Duval, H.L.N.; Sire, O.; Le Tilly, V.R. Investigating the in vitro thermal stability and conformational flexibility of estrogen receptors as potential key factors of their in vivo activity. Biochemistry, 2015, 54(25), 3890-3900.
[54]
Dunlap, T.L.; Howell, C.E.; Mukand, N.; Chen, S-N.; Pauli, G.F.; Dietz, B.M.; Bolton, J.L. Red clover aryl hydrocarbon receptor (AhR) and Estrogen Receptor (ER) agonists enhance genotoxic estrogen metabolism. Chem. Res. Toxicol., 2017, 30(11), 2084-2092.
[55]
Maruthanila, V.; Elancheran, R.; Kunnumakkara, A.; Kabilan, S.; Kotoky, J. Recent development of targeted approaches for the treatment of breast cancer. Breast Cancer, 2017, 24(2), 191-219.
[56]
Kelly, P.M.; Keely, N.O.; Bright, S.A.; Yassin, B.; Ana, G.; Fayne, D.; Zisterer, D.M.; Meegan, M.J. Novel selective estrogen receptor ligand conjugates incorporating endoxifen-combretastatin and cyclofenil-combretastatin hybrid scaffolds: Synthesis and biochemical evaluation. Molecules, 2017, 22(9), 1440.
[57]
Kelly, P.M.; Bright, S.A.; Fayne, D.; Pollock, J.K.; Zisterer, D.M.; Williams, D.C.; Meegan, M.J. Synthesis, antiproliferative and pro-apoptotic activity of 2-phenylindoles. Bioorg. Med. Chem., 2016, 24(18), 4075-4099.
[58]
Singla, R.; Gupta, K.B.; Upadhyay, S.; Dhiman, M.; Jaitak, V. Design, synthesis and biological evaluation of novel indole-benzimidazole hybrids targeting estrogen receptor alpha (ER-α). Eur. J. Med. Chem., 2018, 146, 206-219.
[59]
Eto, R.; Misawa, T.; Noguchi-Yachide, T.; Ohoka, N.; Kurihara, M.; Naito, M.; Tanaka, M.; Demizu, Y. Design and synthesis of estrogen receptor ligands with a 4-heterocycle-4-phenylheptane skeleton. Bioorg. Med. Chem., 2018, 26(8), 1638-1642.
[60]
Singla, R.; Gupta, K.B.; Upadhyay, S.; Dhiman, M.; Jaitak, V. Design, synthesis and biological evaluation of novel indole-xanthendione hybrids as selective estrogen receptor modulators. Bioorg. Med. Chem., 2018, 26(1), 266-277.
[61]
Singla, R.; Prakash, K.; Gupta, K.B.; Upadhyay, S.; Dhiman, M.; Jaitak, V. Identification of novel indole based heterocycles as selective estrogen receptor modulator. Bioorg. Chem., 2018, 79, 72-88.
[62]
De Savi, C.; Bradbury, R.H.; Rabow, A.A.; Norman, R.A.; de Almeida, C.; Andrews, D.M.; Ballard, P.; Buttar, D.; Callis, R.J.; Currie, G.S. Optimization of a novel binding motif to (E)-3-(3, 5-difluoro-4-((1 R, 3 R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2, 3, 4, 9-tetrahydro-1 H-pyrido [3, 4-b] indol-1-yl) phenyl) acrylic Acid (AZD9496), a potent and orally bioavailable selective estrogen receptor downregulator and antagonist. J. Med. Chem., 2015, 58(20), 8128-8140.
[63]
de Oliveira, J.F.; Lima, T.S.; Vendramini-Costa, D.B.; de Lacerda Pedrosa, S.C.B.; Lafayette, E.A.; da Silva, R.M.F.; de Almeida, S.M.V.; de Moura, R.O.; Ruiz, A.L.T.G.; de Carvalho, J.E. Thiosemicarbazones and 4-thiazolidinones indole-based derivatives: Synthesis, evaluation of antiproliferative activity, cell death mechanisms and topoisomerase inhibition assay. Eur. J. Med. Chem., 2017, 136, 305-314.
[64]
Lafayette, E.A.; de Almeida, S.M.V.; Santos, R.V.C.; de Oliveira, J.F.; da Cruz Amorim, C.A.; da Silva, R.M.F.; da Rocha Pitta, M.G.; da Rocha Pitta, I.; de Moura, R.O.; de Carvalho, Junior, L.B. Synthesis of novel indole derivatives as promising DNA-binding agents and evaluation of antitumor and antitopoisomerase I activities. Eur. J. Med. Chem., 2017, 136, 511-522.
[65]
Arora, S.; Agarwal, S.; Singhal, S. Anticancer activities of thiosemicarbazides/thiosemicarbazones: A review. Structure, 2014, 2, R3.
[66]
de Oliveira, J.F.; da Silva, A.L.; Vendramini-Costa, D.B.; da Cruz Amorim, C.A.; Campos, J.F.; Ribeiro, A.G.; de Moura, R.O.; Neves, J.L.; Ruiz, A.L.T.G.; de Carvalho, J.E. Synthesis of thiophene-thiosemicarbazone derivatives and evaluation of their in vitro and in vivo antitumor activities. Eur. J. Med. Chem., 2015, 104, 148-156.
[67]
Krishan, S.; Richardson, D.R.; Sahni, S. The anticancer agent, di-2-pyridylketone 4, 4-dimethyl-3-thiosemicarbazone (Dp44mT), up-regulates the AMPK-dependent energy homeostasis pathway in cancer cells. BBA-Mol. Cell Res., 2016, 1863(12), 2916-2933.
[68]
de Almeida, S.M.V.; Lafayette, E.A.; da Silva, L.P.B.G.; Amorim, C.A.D.C.; de Oliveira, T.B.; Ruiz, A.L.T.G.; de Carvalho, J.E.; de Moura, R.O.; Beltrão, E.I.C.; de Lima, M.D.C.A. Synthesis, DNA binding, and antiproliferative activity of novel acridine-thiosemicarbazone derivatives. Int. J. Mol. Sci., 2015, 16(6), 13023-13042.
[69]
Merlot, A.M.; Shafie, N.H.; Yu, Y.; Richardson, V.; Jansson, P.J.; Sahni, S.; Lane, D.J.; Kovacevic, Z.; Kalinowski, D.S.; Richardson, D.R. Mechanism of the induction of endoplasmic reticulum stress by the anti-cancer agent, di-2-pyridylketone 4, 4-dimethyl-3-thiosemicarbazone (Dp44mT): Activation of PERK/eIF2α, IRE1α, ATF6 and calmodulin kinase. Biochem. Pharmacol., 2016, 109, 27-47.
[70]
Huang, H.; Chen, Q.; Ku, X.; Meng, L.; Lin, L.; Wang, X.; Zhu, C.; Wang, Y.; Chen, Z.; Li, M. A series of α-heterocyclic carboxaldehyde thiosemicarbazones inhibit topoisomerase IIα catalytic activity. J. Med. Chem., 2010, 53(8), 3048-3064.
[71]
Li, X.; Wang, Q.; Qing, Y.; Lin, Y.; Zhang, Y.; Qian, X.; Cui, J. Novel DNA intercalators without basic side chains as efficient antitumor agents: Design, synthesis and evaluation of benzo-[c, d]-indol-malononitrile derivatives. Bioorg. Med. Chem., 2010, 18(9), 3279-3284.
[72]
Azizmohammadi, M.; Khoobi, M.; Ramazani, A.; Emami, S.; Zarrin, A.; Firuzi, O.; Miri, R.; Shafiee, A. 2H-chromene derivatives bearing thiazolidine-2, 4-dione, rhodanine or hydantoin moieties as potential anticancer agents. Eur. J. Med. Chem., 2013, 59, 15-22.
[73]
Lafayette, E.A.; Vitalino de Almeida, S.M.; da Rocha Pitta, M.G.; Carneiro Beltrão, E.I.; Gonçalves da Silva, T.; Olímpio de Moura, R.; da Rocha Pitta, I.; de Carvalho, L.B.; do Carmo Alves de Lima, M. Synthesis, DNA binding and topoisomerase I inhibition activity of thiazacridine and imidazacridine derivatives. Molecules, 2013, 18(12), 15035-15050.
[74]
Majumdar, P.; Bathula, C.; Basu, S.M.; Das, S.K.; Agarwal, R.; Hati, S.; Singh, A.; Sen, S.; Das, B.B. Design, synthesis and evaluation of thiohydantoin derivatives as potent topoisomerase I (Top1) inhibitors with anticancer activity. Eur. J. Med. Chem., 2015, 102, 540-551.
[75]
Shah, A.; Nosheen, E.; Munir, S.; Badshah, A.; Qureshi, R.; Muhammad, N.; Hussain, H. Characterization and DNA binding studies of unexplored imidazolidines by electronic absorption spectroscopy and cyclic voltammetry. J. Photochem. Photobiol. B, 2013, 120, 90-97.
[76]
Zhang, Z.; Bi, C.; Schmitt, S.M.; Fan, Y.; Dong, L.; Zuo, J.; Dou, Q.P. 1, 10-Phenanthroline promotes copper complexes into tumor cells and induces apoptosis by inhibiting the proteasome activity. J. Biol. Inorg. Chem., 2012, 17(8), 1257-1267.
[77]
Zhang, Z.; Wang, H.; Wang, Q.; Yan, M.; Wang, H.; Bi, C.; Sun, S.; Fan, Y. Anticancer activity and computational modeling of ternary copper (II) complexes with 3-indolecarboxylic acid and 1, 10-phenanthroline. Int. J. Oncol., 2016, 49(2), 691-699.
[78]
Wang, X.; Yan, M.; Wang, Q.; Wang, H.; Wang, Z.; Zhao, J.; Li, J.; Zhang, Z. In vitro DNA-binding, anti-oxidant and anticancer activity of indole-2-carboxylic acid dinuclear copper (II) complexes. Molecules, 2017, 22(1), 171.
[79]
Venkatadri, R.; Muni, T.; Iyer, A.; Yakisich, J.; Azad, N. Role of apoptosis-related miRNAs in resveratrol-induced breast cancer cell death. Cell Death Dis., 2017, 7(2), e2104.
[80]
Shen, S.; Li, W.; Ouyang, M-A.; Wang, J. Structure-activity relationship of Triterpenes and derived Glycosides against cancer cells and mechanism of apoptosis induction. Nat. Prod. Res., 2018, 32(6), 654-661.
[81]
Matsuura, K.; Canfield, K.; Feng, W.; Kurokawa, M. Metabolic regulation of apoptosis in cancer.In: International Review of Cell and Molecular Biology; Elsevier, 2016, Vol. 327, pp. 43-87.
[82]
Liu, Q.; Cao, Y.; Zhou, P.; Gui, S.; Wu, X.; Xia, Y.; Tu, J. Panduratin a inhibits cell proliferation by inducing G0/G1 phase cell cycle arrest and induces apoptosis in breast cancer cells. Biomol. Ther., 2018, 26(3), 328.
[83]
Eldehna, W.M.; Almahli, H.; Al-Ansary, G.H.; Ghabbour, H.A.; Aly, M.H.; Ismael, O.E.; Al-Dhfyan, A.; Abdel-Aziz, H.A. Synthesis and in vitro anti-proliferative activity of some novel isatins conjugated with quinazoline/phthalazine hydrazines against triple-negative breast cancer MDA-MB-231 cells as apoptosis-inducing agents. J. Enzyme Inhib. Med. Chem., 2017, 32(1), 600-613.
[84]
Kamath, P.R.; Sunil, D.; Ajees, A.A.; Pai, K.; Biswas, S.N. ′-((2-(6-bromo-2-oxo-2H-chromen-3-yl)-1H-indol-3-yl) methylene) benzohydrazide as a probable Bcl-2/Bcl-xL inhibitor with apoptotic and anti-metastatic potential. Eur. J. Med. Chem., 2016, 120, 134-147.
[85]
Prajapti, S.K.; Nagarsenkar, A.; Guggilapu, S.D.; Gupta, K.K.; Allakonda, L.; Jeengar, M.K.; Naidu, V.; Babu, B.N. Synthesis and biological evaluation of oxindole linked indolyl-pyrimidine derivatives as potential cytotoxic agents. Bioorg. Med. Chem. Lett., 2016, 26(13), 3024-3028.
[86]
Nikalje, A.P.G.; Tiwari, S.V.; Sangshetti, J.N.; Damale, M.D. Ultrasound-mediated synthesis, biological evaluation, docking and in vivo acute oral toxicity study of novel indolin-2-one coupled pyrimidine derivatives. Res. Chem. Intermed., 2018, 44(5), 3031-3059.
[87]
Jowett, L.A.; Howe, E.N.; Soto-Cerrato, V.; Rossom, W.; Pérez-Tomás, R.; Gale, P.A. Indole-based perenosins as highly potent HCl transporters and potential anti-cancer agents. Sci. Rep., 2017, 7(1), 9397.
[88]
Haider, S.; Alam, M.S.; Hamid, H. 1, 3, 4-Thiadiazoles: A potent multi targeted pharmacological scaffold. Eur. J. Med. Chem., 2015, 92, 156-177.
[89]
Kamath, P.R.; Sunil, D.; Joseph, M.M.; Salam, A.A.A.; Sreelekha, T. Indole-coumarin-thiadiazole hybrids: An appraisal of their MCF-7 cell growth inhibition, apoptotic, antimetastatic and computational Bcl-2 binding potential. Eur. J. Med. Chem., 2017, 136, 442-451.
[90]
Chakraborty, S.; Ghosh, S.; Banerjee, B.; Santra, A.; Adhikary, A.; Misra, A.K.; Sen, P.C. Phemindole, a synthetic di-indole derivative maneuvers the store operated calcium entry (SOCE) to induce potent anti-carcinogenic activity in human triple negative breast cancer cells. Front. Pharmacol., 2016, 7, 114.
[91]
Ibrahim, H.S.; Abou-Seri, S.M.; Abdel-Aziz, H.A. 3-Hydrazinoindolin-2-one derivatives: chemical classification and investigation of their targets as anticancer agents. Eur. J. Med. Chem., 2016, 122, 366-381.
[92]
Ibrahim, H.S.; Abou-seri, S.M.; Ismail, N.S.; Elaasser, M.M.; Aly, M.H.; Abdel-Aziz, H.A. Bis-isatin hydrazones with novel linkers: Synthesis and biological evaluation as cytotoxic agents. Eur. J. Med. Chem., 2016, 108, 415-422.
[93]
Eldehna, W.M.; Abo-Ashour, M.F.; Ibrahim, H.S.; Al-Ansary, G.H.; Ghabbour, H.A.; Elaasser, M.M.; Ahmed, H.Y.; Safwat, N.A. Novel [(3-indolylmethylene) hydrazono] indolin-2-ones as apoptotic anti-proliferative agents: design, synthesis and in vitro biological evaluation. J. Enzyme Inhib. Med. Chem., 2018, 33(1), 686-700.
[94]
Liang, Z.; Zhang, D.; Ai, J.; Chen, L.; Wang, H.; Kong, X.; Zheng, M.; Liu, H.; Luo, C.; Geng, M. Identification and synthesis of N′-(2-oxoindolin-3-ylidene) hydrazide derivatives against c-Met kinase. Bioorg. Med. Chem. Lett., 2011, 21(12), 3749-3754.
[95]
Hassan, T.A-F.M.; Kadi, A.A.; Abdel-Aziz, H.A-K.N. N, N′- hydrazino-bis-isatin derivatives with selective activity against multidrug-resistant cancer cells. U.S. Patent 8,497,296. 2013.
[96]
Eldehna, W.M. EL-Naggar, D.H.; Hamed, A.R.; Ibrahim, H.S.; Ghabbour, H.A.; Abdel-Aziz, H.A. One-pot three-component synthesis of novel spirooxindoles with potential cytotoxic activity against triple-negative breast cancer MDA-MB-231 cells. J. Enzyme Inhib. Med. Chem., 2018, 33(1), 309-318.
[97]
Su, S.C.; Hsieh, M.J.; Yang, W.E.; Chung, W.H.; Reiter, R.J.; Yang, S.F. Cancer metastasis: Mechanisms of inhibition by melatonin. J. Pineal Res., 2017, 62(1), e12370.
[98]
Gatti, G.; Lucini, V.; Dugnani, S.; Calastretti, A.; Spadoni, G.; Bedini, A.; Rivara, S.; Mor, M.; Canti, G.; Scaglione, F. Antiproliferative and pro-apoptotic activity of melatonin analogues on melanoma and breast cancer cells. Oncotarget, 2017, 8(40), 68338.
[99]
Esposito, L.; Indovina, P.; Magnotti, F.; Conti, D.; Giordano, A. Anticancer therapeutic strategies based on CDK inhibitors. Curr. Pharm. Des., 2013, 19(30), 5327-5332.
[100]
Carbone, A.; Pennati, M.; Barraja, P.; Montalbano, A.; Parrino, B.; Spanò, V.; Lopergolo, A.; Sbarra, S.; Doldi, V.; Zaffaroni, N. Synthesis and antiproliferative activity of substituted 3 [2-(1H-indol-3-yl)-1, 3-thiazol-4-yl]-1H-pyrrolo [3, 2-b] pyridines, marine alkaloid nortopsentin analogues. Curr. Med. Chem., 2014, 21(14), 1654-1666.
[101]
Parrino, B.; Attanzio, A.; Spano, V.; Cascioferro, S.; Montalbano, A.; Barraja, P.; Tesoriere, L.; Diana, P.; Cirrincione, G.; Carbone, A. Synthesis, antitumor activity and CDK1 inhibiton of new thiazole nortopsentin analogues. Eur. J. Med. Chem., 2017, 138, 371-383.
[102]
Ibrahim, A.A.; Al-Noor, T.H. Anticancer activity of new di-nuclear copper (I) Complex. Chem. Mater. Res., 2015, 7, 11-19.
[103]
Belskaya, N.P.; Lugovik, K.I.; Bakulev, V.A.; Bauer, J.; Kitanovic, I.; Holenya, P.; Zakhartsev, M.; Wölfl, S. The new facile and straightforward method for the synthesis of 4H-1, 2, 3-thiadiazolo [5, 4-b] indoles and determination of their antiproliferative activity. Eur. J. Med. Chem., 2016, 108, 245-257.
[104]
Sarma, P.; Bag, I.; Ramaiah, M.J.; Kamal, A.; Bhadra, U.; Pal Bhadra, M. Bisindole-PBD regulates breast cancer cell proliferation via SIRT-p53 axis. Cancer Biol. Ther., 2015, 16(10), 1486-1501.
[105]
Sabbah, D.A.; Hu, J.; Zhong, H.A. Advances in the development of class I phosphoinositide 3-Kinase (PI3K) inhibitors. Curr. Top. Med. Chem., 2016, 16(13), 1413-1426.
[106]
Chakraborty, S.; Ghosh, S.; Banerjee, B.; Santra, A.; Bhat, J.; Adhikary, A.; Chatterjee, S.; Misra, A.K.; Sen, P.C. Mephebrindole, a synthetic indole analog coordinates the crosstalk between p38MAPK and eIF2α/ATF4/CHOP signalling pathways for induction of apoptosis in human breast carcinoma cells. Apoptosis, 2016, 21(10), 1106-1124.
[108]
Sweidan, K.; Sabbah, A.D.; Engelmann, J.; Abdel-Halim, H.; Abu Sheikha, G. Computational docking studies of novel heterocyclic carboxamides as potential PI3Kα inhibitors. Lett. Drug Des. Discov., 2015, 12(10), 856-863.
[109]
Sweidan, K.; Sabbah, D.A.; Bardaweel, S.; Dush, K.A.; Sheikha, G.A.; Mubarak, M.S. Computer-aided design, synthesis, and biological evaluation of new indole-2-carboxamide derivatives as PI3Kα/EGFR inhibitors. Bioorg. Med. Chem. Lett., 2016, 26(11), 2685-2690.
[110]
Rajesh Kumar, M.; Alagumuthu, M.; Violet Dhayabaran, V. N‐substituted hydroxynaphthalene imino‐oxindole derivatives as new class of PI 3‐kinase inhibitor and breast cancer drug: Molecular validation and structure–activity relationship studies. Chem. Biol. Drug Des., 2018, 91(1), 277-284.
[111]
Giusiano, S.; Cochet, C.; Filhol, O.; Duchemin-Pelletier, E.; Secq, V.; Bonnier, P.; Carcopino, X.; Boubli, L.; Birnbaum, D.; Garcia, S. Protein kinase CK2α subunit over-expression correlates with metastatic risk in breast carcinomas: quantitative immunohistochemistry in tissue microarrays. Eur. J. Cancer, 2011, 47(5), 792-801.
[112]
Zhao, T.; Jia, H.; Li, L.; Zhang, G.; Zhao, M.; Cheng, Q.; Zheng, J.; Li, D. Inhibition of CK2 enhances UV-triggered apoptotic cell death in lung cancer cell lines. Oncol. Rep., 2013, 30(1), 377-384.
[113]
Yao, K.; Youn, H.; Gao, X.; Huang, B.; Zhou, F.; Li, B.; Han, H. Casein kinase 2 inhibition attenuates androgen receptor function and cell proliferation in prostate cancer cells. Prostate, 2012, 72(13), 1423-1430.
[114]
Jabor Gozzi, G.; Bouaziz, Z.; Winter, E.; Daflon-Yunes, N.; Aichele, D.; Nacereddine, A.; Marminon, C.; Valdameri, G.; Zeinyeh, W.; Bollacke, A. Converting potent indeno [1, 2-b] indole inhibitors of protein kinase CK2 into selective inhibitors of the breast cancer resistance protein ABCG2. J. Med. Chem., 2014, 58(1), 265-277.
[115]
Galliford, C.V.; Scheidt, K.A. Pyrrolidinyl‐spirooxindole natural products as inspirations for the development of potential therapeutic agents. Angew. Chem. Int. Ed., 2007, 46(46), 8748-8758.
[116]
Ding, K.; Lu, Y.; Nikolovska-Coleska, Z.; Qiu, S.; Ding, Y.; Gao, W.; Stuckey, J.; Krajewski, K.; Roller, P.P.; Tomita, Y. Structure-based design of potent non-peptide MDM2 inhibitors. J. Am. Chem. Soc., 2005, 127(29), 10130-10131.
[117]
Lotfy, G.; El Sayed, H.; Said, M.M.; Aziz, Y.M.A.; Al-Dhfyan, A.; Al-Majid, A.M.; Barakat, A. Regio-and stereoselective synthesis of new spirooxindoles via 1, 3-dipolar cycloaddition reaction: Anticancer and molecular docking studies. J. Photochem. Photobiol. B, 2018, 180, 98-108.
[119]
West, A.C.; Johnstone, R.W. New and emerging HDAC inhibitors for cancer treatment. J. Clin. Invest., 2014, 124(1), 30-39.
[120]
Pruitt, K. Molecular and Cellular Changes During Cancer Progression Resulting From Genetic and Epigenetic Alterations. In: Progress in Molecular Biology and Translational Science; Elsevier, 2016, Vol. 144, pp. 3-47.
[121]
Dokmanovic, M.; Clarke, C.; Marks, P.A. Histone deacetylase inhibitors: Overview and perspectives. Mol. Cancer Res., 2007, 5(10), 981-989.
[122]
Haberland, M.; Montgomery, R.L.; Olson, E.N. The many roles of histone deacetylases in development and physiology: Implications for disease and therapy. Nat. Rev. Genet., 2009, 10(1), 32.
[123]
Witt, O.; Deubzer, H.E.; Milde, T.; Oehme, I. HDAC family: What are the cancer relevant targets? Cancer Lett., 2009, 277(1), 8-21.
[124]
Manna, P.R.; Ahmed, A.U.; Vartak, D.; Molehin, D.; Pruitt, K. Overexpression of the steroidogenic acute regulatory protein in breast cancer: Regulation by histone deacetylase inhibition. Biochem. Biophys. Res. Commun., 2019, 509(2), 476-482.
[125]
Zhang, Y.; Yang, P.; Chou, C.J.; Liu, C.; Wang, X.; Xu, W. Development of N-hydroxycinnamamide-based histone deacetylase inhibitors with an indole-containing cap group. ACS Med. Chem. Lett., 2013, 4(2), 235-238.
[126]
Mehndiratta, S.; Hsieh, Y-L.; Liu, Y-M.; Wang, A.W.; Lee, H-Y.; Liang, L-Y.; Kumar, S.; Teng, C-M.; Yang, C-R.; Liou, J-P. Indole-3-ethylsulfamoylphenylacrylamides: potent histone deacetylase inhibitors with anti-inflammatory activity. Eur. J. Med. Chem., 2014, 85, 468-479.
[127]
Huang, Y-C.; Huang, F-I.; Mehndiratta, S.; Lai, S-C.; Liou, J-P.; Yang, C-R. Anticancer activity of MPT0G157, a derivative of indolylbenzenesulfonamide, inhibits tumor growth and angiogenesis. Oncotarget, 2015, 6(21), 18590.
[128]
Mehndiratta, S.; Pan, S-L.; Kumar, S.; Liou, J-P. Indole-3-ethylsulfamoylphenylacrylamides with Potent Anti-proliferative and Anti-angiogenic Activities. Anticancer. Agents Med. Chem., 2016, 16(7), 907-913.
[129]
Cho, Y.S.; Whitehead, L.; Li, J.; Chen, C.H-T.; Jiang, L.; Vögtle, M.; Francotte, E.; Richert, P.; Wagner, T.; Traebert, M. Conformational refinement of hydroxamate-based histone deacetylase inhibitors and exploration of 3-piperidin-3-ylindole analogues of dacinostat (LAQ824). J. Med. Chem., 2010, 53(7), 2952-2963.
[130]
Mahboobi, S.; Sellmer, A.; Höcher, H.; Garhammer, C.; Pongratz, H.; Maier, T.; Ciossek, T.; Beckers, T. 2-Aroylindoles and 2-aroylbenzofurans with N-hydroxyacrylamide substructures as a novel series of rationally designed histone deacetylase inhibitors. J. Med. Chem., 2007, 50(18), 4405-4418.
[131]
Mehndiratta, S.; Wang, R-S.; Huang, H-L.; Su, C-J.; Hsu, C-M.; Wu, Y-W.; Pan, S-L.; Liou, J-P. 4-Indolyl-N-hydroxyphenylacrylamides as potent HDAC class I and IIB inhibitors in vitro and in vivo. Eur. J. Med. Chem., 2017, 134, 13-23.
[132]
Wang, X.; Li, X.; Li, J.; Hou, J.; Qu, Y.; Yu, C.; He, F.; Xu, W.; Wu, J. Design, synthesis, and preliminary bioactivity evaluation of N1‐hydroxyterephthalamide derivatives with indole cap as novel histone deacetylase inhibitors. Chem. Biol. Drug Des., 2017, 89(1), 38-46.
[133]
Nagarsenkar, A.; Guntuku, L.; Guggilapu, S.D.; Gannoju, S.; Naidu, V.; Bathini, N.B. Synthesis and apoptosis inducing studies of triazole linked 3-benzylidene isatin derivatives. Eur. J. Med. Chem., 2016, 124, 782-793.
[134]
Singh, A.; Saha, S.T.; Perumal, S.; Kaur, M.; Kumar, V. Azide-alkyne cycloaddition en route to 1 H-1, 2, 3-triazole-tethered isatin-ferrocene, ferrocenylmethoxy-isatin, and isatin-ferrocenylchalcone conjugates: Synthesis and antiproliferative evaluation. ACS Omega, 2018, 3(1), 1263-1268.
[135]
Amr, A.E-G.E.; Abdalla, M.M.; Al-Omar, M.A.; Elsayed, E.A. Anti-ovarian and anti-breast cancers with dual topoisomerase ii/braf600e inhibitors activities of some substituted indole derivatives. Biomed. Res., 2017, 28(1), 75-80.
[136]
Ghaidan, A.F.; Faraj, F.L.; Abdulghany, Z.S. Synthesis, characterization and cytotoxic activity of new indole schiff bases derived from 2-(5-chloro-3, 3-dimethyl-1, 3-dihydro-indol-2-ylidene)-malonaldehyde with aniline substituted. Orient. J. Chem., 2018, 34(1), 169-181.
[138]
Gokhale, N.; Dalimba, U.; Kumsi, M. Facile synthesis of indole-pyrimidine hybrids and evaluation of their anticancer and antimicrobial activity. J. Saudi Chem. Soc., 2017, 21(7), 761-775.
[139]
Venkata Ramana, K.; Madhava, G.; Ravendra Babu, K.; Subbarao, D.; Hema Kumar, K.; Naga Raju, C. Synthesis of novel N, N-disubstituted ethyl P-[2-(1 H-Indol-3-YL) acetyl] phosphoramidates and their biological activity. Phosphorus Sulfur Silicon Relat. Elem., 2015, 190(11), 2013-2022.
[140]
Sreenivasulu, R.; Sujitha, P.; Jadav, S.S.; Ahsan, M.J.; Kumar, C.G.; Raju, R.R. Synthesis, antitumor evaluation, and molecular docking studies of indole-indazolyl hydrazide-hydrazone derivatives. Monatsh. Chem., 2017, 148(2), 305-314.
[141]
Murali, K.; Sparkes, H.A.; Prasad, K.J.R. Regio-and stereoselective synthesis of dispirooxindole-pyrrolocarbazole hybrids via 1, 3-dipolar cycloaddition reactions: Cytotoxic activity and SAR studies. Eur. J. Med. Chem., 2018, 143, 292-305.
[142]
Chhabra, M.; Sinha, S.; Banerjee, S.; Paira, P. An efficient green synthesis of 2-arylbenzothiazole analogues as potent antibacterial and anticancer agents. Bioorg. Med. Chem. Lett., 2016, 26(1), 213-217.
[143]
Van Rossom, W.; Asby, D.J.; Tavassoli, A.; Gale, P.A. Perenosins: a new class of anion transporter with anti-cancer activity. Org. Biomol. Chem., 2016, 14(9), 2645-2650.
[144]
Debnath, B.; Ganguly, S. Synthesis, biological evaluation, in silico docking, and virtual ADME studies of 2-[2-Oxo-3-(arylimino) indolin-1-yl]-N-arylacetamides as potent anti-breast cancer agents. Monatsh. Chem., 2016, 147(3), 565-574.
[145]
Vaddula, B.R.; Tantak, M.P.; Sadana, R.; Gonzalez, M.A.; Kumar, D. One-pot synthesis and in-vitro anticancer evaluation of 5-(2′-indolyl) thiazoles. Sci. Rep., 2016, 6, 23401.
Related Journals
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
Current Bioactive Compounds
Current Cancer Drug Targets
Current Cancer Therapy Reviews
Current Drug Safety
Current Drug Targets
Recent Patents on Anti-Cancer Drug Discovery
Letters in Drug Design & Discovery
Current Drug Discovery Technologies
Current Radiopharmaceuticals
Related Books
Science of Spices and Culinary Herbs - Latest Laboratory, Pre-clinical, and Clinical Studies
Frontiers in Clinical Drug Research - Anti-Cancer Agents
Advances in Organic Synthesis
Frontiers in Natural Product Chemistry
Recent Advances in Analytical Techniques
Frontiers in Drug Design and Discovery
NEOPLASIA and FERTILITY
Therapeutic Use of Plant Secondary Metabolites
Frontiers in Computational Chemistry
Frontiers in Bioactive Compounds
Article Metrics
95
9