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Current Organic Chemistry

Author(s): Reyaz Hassan Mir*, Roohi Mohi-ud-din, Taha Umair Wani, Mohammad Ovais Dar, Abdul Jaleel Shah, Bashir Lone, Chawla Pooja and Mubashir Hussain Masoodi*

DOI: 10.2174/1385272825666210208142108

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Indole: A Privileged Heterocyclic Moiety in the Management of Cancer

Page: [724 - 736] Pages: 13

  • * (Excluding Mailing and Handling)

Abstract

Heterocyclic are a class of compounds that are intricately entwined into life processes. Almost more than 90% of marketed drugs carry heterocycles. Synthetic chemistry, in turn, allocates a cornucopia of heterocycles. Among the heterocycles, indole, a bicyclic structure consisting of a six-membered benzene ring fused to a five-membered pyrrole ring with numerous pharmacophores that generate a library of various lead molecules. Due to its profound pharmacological profile, indole got wider attention around the globe to explore it fully in the interest of mankind. The current review covers recent advancements on indole in the design of various anti-cancer agents acting by targeting various enzymes or receptors, including (HDACs), sirtuins, PIM kinases, DNA topoisomerases, and σ receptors.

Keywords: Heterocycles, anti-cancer, cytotoxic activity, drug design, PIM kinases, DNA topoisomerases.

Graphical Abstract

[1]
Azad, I.; Nasibullah, M.; Khan, T.; Hassan, F.; Akhter, Y. Exploring the novel heterocyclic derivatives as lead molecules for design and development of potent anticancer agents. J. Mol. Graph. Model., 2018, 81, 211-228.
[http://dx.doi.org/10.1016/j.jmgm.2018.02.013] [PMID: 29609141]
[2]
Martins, P.; Jesus, J.; Santos, S.; Raposo, L.R.; Roma-Rodrigues, C.; Baptista, P.V.; Fernandes, A.R. Heterocyclic anticancer compounds: recent advances and the paradigm shift towards the use of nanomedicine’s tool box. Molecules, 2015, 20(9), 16852-16891.
[http://dx.doi.org/10.3390/molecules200916852] [PMID: 26389876]
[3]
Kaur, N.; Bhardwaj, P.; Devi, M.; Verma, Y.; Ahlawat, N.; Grewal, P. Ionic liquids for the synthesis of five-membered N, N-, N, N, N-and N, N, N, N-heterocycles. Curr. Org. Chem., 2019, 23, 1214-1238.
[http://dx.doi.org/10.2174/1385272823666190717101741]
[4]
Sherer, C.; Snape, T.J. Heterocyclic scaffolds as promising anticancer agents against tumours of the central nervous system: exploring the scope of indole and carbazole derivatives. Eur. J. Med. Chem., 2015, 97, 552-560.
[http://dx.doi.org/10.1016/j.ejmech.2014.11.007] [PMID: 25466446]
[5]
Brancale, A.; Silvestri, R. Indole, a core nucleus for potent inhibitors of tubulin polymerization. Med. Res. Rev., 2007, 27(2), 209-238.
[http://dx.doi.org/10.1002/med.20080] [PMID: 16788980]
[6]
Pearce, S. The importance of heterocyclic compounds in anti-cancer drug design. Drug Discov., 2017, 2017, 67.
[7]
Ahmad, A.; Sakr, W.A.; Rahman, K.M. Anticancer properties of indole compounds: mechanism of apoptosis induction and role in chemotherapy. Curr. Drug Targets, 2010, 11(6), 652-666.
[http://dx.doi.org/10.2174/138945010791170923] [PMID: 20298156]
[8]
Mphahlele, M.J.; Makhafola, T.J.; Mmonwa, M.M. In vitro cytotoxicity of novel 2,5,7-tricarbo-substituted indoles derived from 2-amino-5-bromo-3-iodoacetophenone. Bioorg. Med. Chem., 2016, 24(19), 4576-4586.
[http://dx.doi.org/10.1016/j.bmc.2016.07.056] [PMID: 27499368]
[9]
Zakharova, O.; Nevinsky, G.; Politanskaya, L.; Baev, D.; Ovchinnikova, L.; Tretyakov, E. Evaluation of antioxidant activity and cytotoxicity of polyfluorinated diarylacetylenes and indoles toward human cancer cells. J. Fluor. Chem., 2019, 226109353
[http://dx.doi.org/10.1016/j.jfluchem.2019.109353]
[10]
Bakherad, Z.; Safavi, M.; Fassihi, A.; Sadeghi-Aliabadi, H.; Bakherad, M.; Rastegar, H.; Saeedi, M.; Ghasemi, J.B.; Saghaie, L.; Mahdavi, M. Design and synthesis of novel cytotoxic indole-thiosemicarbazone derivatives: biological evaluation and docking study. Chem. Biodivers., 2019, 16(4)e1800470
[http://dx.doi.org/10.1002/cbdv.201800470] [PMID: 30845369]
[11]
Heravi, M.M.; Moradi, R.; Malmir, M. Recent advances in the application of the Heck reaction in the synthesis of heterocyclic compounds: an update. Curr. Org. Chem., 2018, 22, 165-198.
[http://dx.doi.org/10.2174/1385272821666171002121126]
[12]
Megna, B.W.; Carney, P.R.; Nukaya, M.; Geiger, P.; Kennedy, G.D. Indole-3-carbinol induces tumor cell death: function follows form. J. Surg. Res., 2016, 204(1), 47-54.
[http://dx.doi.org/10.1016/j.jss.2016.04.021] [PMID: 27451867]
[13]
Katz, E.; Nisani, S.; Chamovitz, D.A. Indole-3-carbinol: a plant hormone combatting cancer. F1000Research, 2018, 7, 689.
[14]
Ge, X.; Yannai, S.; Rennert, G.; Gruener, N.; Fares, F.A. 3,3′-Diindolylmethane induces apoptosis in human cancer cells. Biochem. Biophys. Res. Commun., 1996, 228(1), 153-158.
[http://dx.doi.org/10.1006/bbrc.1996.1631] [PMID: 8912651]
[15]
Xing, L.; Zhang, Y.; Du, Y. Hypervalent iodine-mediated synthesis of spiroheterocycles via oxidative cyclization. Curr. Org. Chem., 2019, 23, 14-37.
[http://dx.doi.org/10.2174/1385272822666181211122802]
[16]
Rahman, K.M.; Li, Y.; Sarkar, F.H. Inactivation of akt and NF-kappaB play important roles during indole-3-carbinol-induced apoptosis in breast cancer cells. Nutr. Cancer, 2004, 48(1), 84-94.
[http://dx.doi.org/10.1207/s15327914nc4801_12] [PMID: 15203382]
[17]
Kong, D.; Li, Y.; Wang, Z.; Banerjee, S.; Sarkar, F.H. Inhibition of angiogenesis and invasion by 3,3′-diindolylmethane is mediated by the nuclear factor-kappaB downstream target genes MMP-9 and uPA that regulated bioavailability of vascular endothelial growth factor in prostate cancer. Cancer Res., 2007, 67(7), 3310-3319.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-4277] [PMID: 17409440]
[18]
Banerjee, S.; Wang, Z.; Kong, D.; Sarkar, F.H. 3,3′-Diindolylmethane enhances chemosensitivity of multiple chemotherapeutic agents in pancreatic cancer. Cancer Res., 2009, 69(13), 5592-5600.
[http://dx.doi.org/10.1158/0008-5472.CAN-09-0838] [PMID: 19531648]
[19]
Chinni, S.R.; Li, Y.; Upadhyay, S.; Koppolu, P.K.; Sarkar, F.H. Indole-3-carbinol (I3C) induced cell growth inhibition, G1 cell cycle arrest and apoptosis in prostate cancer cells. Oncogene, 2001, 20(23), 2927-2936.
[http://dx.doi.org/10.1038/sj.onc.1204365] [PMID: 11420705]
[20]
Rahman, K.M.; Sarkar, F.H. Steroid hormone mimics: molecular mechanisms of cell growth and apoptosis in normal and malignant mammary epithelial cells. J. Steroid Biochem. Mol. Biol., 2002, 80(2), 191-201.
[http://dx.doi.org/10.1016/S0960-0760(01)00186-8] [PMID: 11897503]
[21]
Chinni, S.R.; Sarkar, F.H. Akt inactivation is a key event in indole-3- carbinol-induced apoptosis in PC-3 cells. Clin. Cancer Res, 2002, 8(4), 1228-1236.
[PMID: 11948137]
[22]
Rahman, K.W.; Li, Y.; Wang, Z.; Sarkar, S.H.; Sarkar, F.H. Gene expression profiling revealed survivin as a target of 3,3′-diindolylmethane-induced cell growth inhibition and apoptosis in breast cancer cells. Cancer Res., 2006, 66(9), 4952-4960.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-3918] [PMID: 16651453]
[23]
Wang, Z.; Yu, B.W.; Rahman, K.M.; Ahmad, F.; Sarkar, F.H. Induction of growth arrest and apoptosis in human breast cancer cells by 3,3-diindolylmethane is associated with induction and nuclear localization of p27kip. Mol. Cancer Ther., 2008, 7(2), 341-349.
[http://dx.doi.org/10.1158/1535-7163.MCT-07-0476] [PMID: 18281517]
[24]
Firestone, G.L.; Bjeldanes, L.F. Indole-3-carbinol and 3-3′-diindolylmethane antiproliferative signaling pathways control cell-cycle gene transcription in human breast cancer cells by regulating promoter-Sp1 transcription factor interactions. J. Nutr., 2003, 133(7), 2448S-2455S.
[http://dx.doi.org/10.1093/jn/133.7.2448S] [PMID: 12840223]
[25]
Vivar, O.I.; Lin, C-L.; Firestone, G.L.; Bjeldanes, L.F. 3,3′-Diindolyl-methane induces a G(1) arrest in human prostate cancer cells irrespective of androgen receptor and p53 status. Biochem. Pharmacol., 2009, 78(5), 469-476.
[http://dx.doi.org/10.1016/j.bcp.2009.05.008] [PMID: 19433067]
[26]
Rahman, K.M.; Banerjee, S.; Ali, S.; Ahmad, A.; Wang, Z.; Kong, D.; Sakr, W.A. 3,3′-Diindolylmethane enhances taxotere-induced apoptosis in hormone-refractory prostate cancer cells through survivin down-regulation. Cancer Res., 2009, 69(10), 4468-4475.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-4423] [PMID: 19435906]
[27]
McGuire, K.P.; Ngoubilly, N.; Neavyn, M.; Lanza-Jacoby, S. 3,3′-diindolyl-methane and paclitaxel act synergistically to promote apoptosis in HER2/Neu human breast cancer cells. J. Surg. Res., 2006, 132(2), 208-213.
[http://dx.doi.org/10.1016/j.jss.2006.02.008] [PMID: 16580691]
[28]
Stünkel, W.; Campbell, R.M. Sirtuin 1 (SIRT1): the misunderstood HDAC. J. Biomol. Screen., 2011, 16(10), 1153-1169.
[http://dx.doi.org/10.1177/1087057111422103] [PMID: 22086720]
[29]
Moore, R.L.; Dai, Y.; Faller, D.V. Sirtuin 1 (SIRT1) and steroid hormone receptor activity in cancer. J. Endocrinol., 2012, 213(1), 37-48.
[http://dx.doi.org/10.1530/JOE-11-0217] [PMID: 22159506]
[30]
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]
[31]
Zhou, Z.; Ma, T.; Zhu, Q.; Xu, Y.; Zha, X. Recent advances in inhibitors of sirtuin1/2: an update and perspective. Future Med. Chem., 2018, 10(8), 907-934.
[http://dx.doi.org/10.4155/fmc-2017-0207] [PMID: 29642711]
[32]
Rambabu, D.; Raja, G.; Yogi Sreenivas, B.; Seerapu, G.P.; Lalith Kumar, K.; Deora, G.S.; Haldar, D.; Rao, M.V.; Pal, M. Spiro heterocycles as potential inhibitors of SIRT1: Pd/C-mediated synthesis of novel N-indolylmethyl spiroindoline-3,2′-quinazolines. Bioorg. Med. Chem. Lett., 2013, 23(5), 1351-1357.
[http://dx.doi.org/10.1016/j.bmcl.2012.12.089] [PMID: 23410798]
[33]
Panathur, N.; Dalimba, U.; Koushik, P.V.; Alvala, M.; Yogeeswari, P.; Sriram, D.; Kumar, V. Identification and characterization of novel indole based small molecules as anticancer agents through SIRT1 inhibition. Eur. J. Med. Chem., 2013, 69, 125-138.
[http://dx.doi.org/10.1016/j.ejmech.2013.08.018] [PMID: 24013412]
[34]
Panathur, N.; Gokhale, N.; Dalimba, U.; Koushik, P.V.; Yogeeswari, P.; Sriram, D. New indole-isoxazolone derivatives: synthesis, characterisation and in vitro SIRT1 inhibition studies. Bioorg. Med. Chem. Lett., 2015, 25(14), 2768-2772.
[http://dx.doi.org/10.1016/j.bmcl.2015.05.015] [PMID: 26025875]
[35]
Manjula, R.; Gokhale, N.; Unni, S.; Deshmukh, P.; Reddyrajula, R.; Srinivas Bharath, M.M.; Dalimba, U.; Padmanabhan, B. Design, synthesis, in-vitro evaluation and molecular docking studies of novel indole derivatives as inhibitors of SIRT1 and SIRT2. Bioorg. Chem., 2019, 92103281
[http://dx.doi.org/10.1016/j.bioorg.2019.103281] [PMID: 31561106]
[36]
Laaroussi, H.; Ding, Y.; Teng, Y.; Deschamps, P.; Vidal, M.; Yu, P.; Broussy, S. Synthesis of indole inhibitors of silent information regulator 1 (SIRT1), and their evaluation as cytotoxic agents. Eur. J. Med. Chem., 2020, 202112561
[http://dx.doi.org/10.1016/j.ejmech.2020.112561] [PMID: 32711231]
[37]
Luszczak, S.; Kumar, C.; Sathyadevan, V.K.; Simpson, B.S.; Gately, K.A.; Whitaker, H.C.; Heavey, S. PIM kinase inhibition: co-targeted therapeutic approaches in prostate cancer. Signal Transduct. Target. Ther., 2020, 5(1), 7.
[http://dx.doi.org/10.1038/s41392-020-0109-y] [PMID: 32296034]
[38]
Haddach, M.; Michaux, J.; Schwaebe, M.K.; Pierre, F.; O’Brien, S.E.; Borsan, C.; Tran, J.; Raffaele, N.; Ravula, S.; Drygin, D.; Siddiqui-Jain, A.; Darjania, L.; Stansfield, R.; Proffitt, C.; Macalino, D.; Streiner, N.; Bliesath, J.; Omori, M.; Whitten, J.P.; Anderes, K.; Rice, W.G.; Ryckman, D.M. Discovery of CX-6258. A potent, selective, and orally efficacious pan-Pim kinases inhibitor. ACS Med. Chem. Lett., 2011, 3(2), 135-139.
[http://dx.doi.org/10.1021/ml200259q] [PMID: 24900437]
[39]
Nishiguchi, G.A.; Atallah, G.; Bellamacina, C.; Burger, M.T.; Ding, Y.; Feucht, P.H.; Garcia, P.D.; Han, W.; Klivansky, L.; Lindvall, M. Discovery of novel 3,5-disubstituted indole derivatives as potent inhibitors of Pim-1, Pim-2, and Pim-3 protein kinases. Bioorg. Med. Chem. Lett., 2011, 21(21), 6366-6369.
[http://dx.doi.org/10.1016/j.bmcl.2011.08.105] [PMID: 21945284]
[40]
More, K.N.; Jang, H.W.; Hong, V.S.; Lee, J. Pim kinase inhibitory and antiproliferative activity of a novel series of meridianin C derivatives. Bioorg. Med. Chem. Lett., 2014, 24(11), 2424-2428.
[http://dx.doi.org/10.1016/j.bmcl.2014.04.035] [PMID: 24775304]
[41]
More, K.N.; Hong, V.S.; Lee, A.; Park, J.; Kim, S.; Lee, J. Discovery and evaluation of 3,5-disubstituted indole derivatives as Pim kinase inhibitors. Bioorg. Med. Chem. Lett., 2018, 28(14), 2513-2517.
[http://dx.doi.org/10.1016/j.bmcl.2018.05.054] [PMID: 29871845]
[42]
Wu, B.; Wang, H-L.; Cee, V.J.; Lanman, B.A.; Nixey, T.; Pettus, L.; Reed, A.B.; Wurz, R.P.; Guerrero, N.; Sastri, C.; Winston, J.; Lipford, J.R.; Lee, M.R.; Mohr, C.; Andrews, K.L.; Tasker, A.S. Discovery of 5-(1H-indol-5-yl)-1,3,4-thiadiazol-2-amines as potent PIM inhibitors. Bioorg. Med. Chem. Lett., 2015, 25(4), 775-780.
[http://dx.doi.org/10.1016/j.bmcl.2014.12.091] [PMID: 25616902]
[43]
Wurz, R.P.; Pettus, L.H.; Jackson, C.; Wu, B.; Wang, H-L.; Herberich, B.; Cee, V.; Lanman, B.A.; Reed, A.B.; Chavez, F., Jr; Nixey, T.; Laszlo, J., III; Wang, P.; Nguyen, Y.; Sastri, C.; Guerrero, N.; Winston, J.; Lipford, J.R.; Lee, M.R.; Andrews, K.L.; Mohr, C.; Xu, Y.; Zhou, Y.; Reid, D.L.; Tasker, A.S. The discovery and optimization of aminooxadiazoles as potent Pim kinase inhibitors. Bioorg. Med. Chem. Lett., 2015, 25(4), 847-855.
[http://dx.doi.org/10.1016/j.bmcl.2014.12.067] [PMID: 25599837]
[44]
Quirion, R.; Bowen, W.D.; Itzhak, Y.; Junien, J.L.; Musacchio, J.M.; Rothman, R.B.; Su, T.P.; Tam, S.W.; Taylor, D.P. A proposal for the classification of sigma binding sites. Trends Pharmacol. Sci., 1992, 13(3), 85-86.
[http://dx.doi.org/10.1016/0165-6147(92)90030-A] [PMID: 1315463]
[45]
Su, T-P.; Hayashi, T.; Maurice, T.; Buch, S.; Ruoho, A.E. The sigma-1 receptor chaperone as an inter-organelle signaling modulator. Trends Pharmacol. Sci., 2010, 31(12), 557-566.
[http://dx.doi.org/10.1016/j.tips.2010.08.007] [PMID: 20869780]
[46]
Hayashi, T.; Su, T-P. Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca2+ signaling and cell survival. Cell, 2007, 131(3), 596-610.
[http://dx.doi.org/10.1016/j.cell.2007.08.036] [PMID: 17981125]
[47]
Volz, H-P.; Stoll, K.D. Clinical trials with sigma ligands. Pharmacopsychiatry, 2004, 37(Suppl. 3), S214-S220.
[http://dx.doi.org/10.1055/s-2004-832680] [PMID: 15547788]
[48]
Bourrie, B.; Bribes, E.; Derocq, J-M.; Vidal, H.; Casellas, P. Sigma receptor ligands: applications in inflammation and oncology. Current.Opin. Investig. Drugs, 2004, 5, 1158-1163.
[PMID: 15573866]
[49]
Maurice, T.; Su, T-P. The pharmacology of sigma-1 receptors. Pharmacol. Ther., 2009, 124(2), 195-206.
[http://dx.doi.org/10.1016/j.pharmthera.2009.07.001] [PMID: 19619582]
[50]
Villard, V.; Espallergues, J.; Keller, E.; Alkam, T.; Nitta, A.; Yamada, K.; Nabeshima, T.; Vamvakides, A.; Maurice, T. Antiamnesic and neuroprotective effects of the aminotetrahydrofuran derivative ANAVEX1-41 against amyloid β(25-35)-induced toxicity in mice. Neuropsychopharmacology, 2009, 34(6), 1552-1566.
[http://dx.doi.org/10.1038/npp.2008.212] [PMID: 19052542]
[51]
Vilner, B.J.; John, C.S.; Bowen, W.D. Sigma-1 and sigma-2 receptors are expressed in a wide variety of human and rodent tumor cell lines. Cancer Res., 1995, 55(2), 408-413.
[PMID: 7812973]
[52]
van Waarde, A.; Rybczynska, A.A.; Ramakrishnan, N.; Ishiwata, K.; Elsinga, P.H.; Dierckx, R.A.J.O. Sigma receptors in oncology: therapeutic and diagnostic applications of sigma ligands. Curr. Pharm. Des., 2010, 16(31), 3519-3537.
[http://dx.doi.org/10.2174/138161210793563365] [PMID: 21050178]
[53]
Xu, J.; Zeng, C.; Chu, W.; Pan, F.; Rothfuss, J.M.; Zhang, F.; Tu, Z.; Zhou, D.; Zeng, D.; Vangveravong, S.; Johnston, F.; Spitzer, D.; Chang, K.C.; Hotchkiss, R.S.; Hawkins, W.G.; Wheeler, K.T.; Mach, R.H. Identification of the PGRMC1 protein complex as the putative sigma-2 receptor binding site. Nat. Commun., 2011, 2, 380.
[http://dx.doi.org/10.1038/ncomms1386] [PMID: 21730960]
[54]
Heading, C. Siramesine H lundbeck. Curr. Opin. Investig. Drugs, 2001, 2(2), 266-270.
[PMID: 11816842]
[55]
Spirkoski, J.; Melo, F.R.; Grujic, M.; Calounova, G.; Lundequist, A.; Wernersson, S.; Pejler, G. Mast cell apoptosis induced by siramesine, a sigma-2 receptor agonist. Biochem. Pharmacol., 2012, 84(12), 1671-1680.
[http://dx.doi.org/10.1016/j.bcp.2012.09.028] [PMID: 23058984]
[56]
Česen, M.H.; Repnik, U.; Turk, V.; Turk, B. Siramesine triggers cell death through destabilisation of mitochondria, but not lysosomes. Cell Death Dis., 2013, 4, e818-e818.
[http://dx.doi.org/10.1038/cddis.2013.361] [PMID: 24091661]
[57]
Abate, C.; Perrone, R.; Berardi, F. Classes of sigma2 (σ2) receptor ligands: structure affinity relationship (SAfiR) studies and antiproliferative activity. Curr. Pharm. Des., 2012, 18(7), 938-949.
[http://dx.doi.org/10.2174/138161212799436485] [PMID: 22288411]
[58]
Xie, F.; Kniess, T.; Neuber, C.; Deuther-Conrad, W.; Mamat, C.; Lieberman, B.P. Novel indole-based sigma-2 receptor ligands: synthesis, structure–affinity relationship and antiproliferative activity. MedChemComm, 2015, 6, 1093-1103.
[http://dx.doi.org/10.1039/C5MD00079C]
[59]
Korpis, K.; Weber, F.; Brune, S.; Wünsch, B.; Bednarski, P.J. Involvement of apoptosis and autophagy in the death of RPMI 8226 multiple myeloma cells by two enantiomeric sigma receptor ligands. Bioorg. Med. Chem., 2014, 22(1), 221-233.
[http://dx.doi.org/10.1016/j.bmc.2013.11.033] [PMID: 24331758]
[60]
Wang, J.C. Moving one DNA double helix through another by a type II DNA topoisomerase: the story of a simple molecular machine. Q. Rev. Biophys., 1998, 31(2), 107-144.
[http://dx.doi.org/10.1017/S0033583598003424] [PMID: 9794033]
[61]
Wang, J.C. Cellular roles of DNA topoisomerases: a molecular perspective. Nat. Rev. Mol. Cell Biol., 2002, 3(6), 430-440.
[http://dx.doi.org/10.1038/nrm831] [PMID: 12042765]
[62]
Liu, L.F. DNA topoisomerase poisons as antitumor drugs. Annu. Rev. Biochem., 1989, 58, 351-375.
[http://dx.doi.org/10.1146/annurev.bi.58.070189.002031] [PMID: 2549853]
[63]
Sinha, B.K. Topoisomerase inhibitors. A review of their therapeutic potential in cancer. Drugs, 1995, 49(1), 11-19.
[http://dx.doi.org/10.2165/00003495-199549010-00002] [PMID: 7705211]
[64]
Lerman, L.S. Structural considerations in the interaction of DNA and acridines. J. Mol. Biol., 1961, 3, 18-30.
[http://dx.doi.org/10.1016/S0022-2836(61)80004-1] [PMID: 13761054]
[65]
Waring, M. Variation of the supercoils in closed circular DNA by binding of antibiotics and drugs: evidence for molecular models involving intercalation. J. Mol. Biol., 1970, 54(2), 247-279.
[http://dx.doi.org/10.1016/0022-2836(70)90429-8] [PMID: 5500444]
[66]
Lerman, L.S. The structure of the DNA-acridine complex. Proc. Natl. Acad. Sci. USA, 1963, 49, 94-102.
[http://dx.doi.org/10.1073/pnas.49.1.94] [PMID: 13929834]
[67]
Pommier, Y.; Leo, E.; Zhang, H.; Marchand, C. DNA topoisomerases and their poisoning by anticancer and antibacterial drugs. Chem. Biol., 2010, 17(5), 421-433.
[http://dx.doi.org/10.1016/j.chembiol.2010.04.012] [PMID: 20534341]
[68]
Fortune, J.M.; Osheroff, N. Topoisomerase II as a target for anticancer drugs: when enzymes stop being nice. Prog. Nucleic Acid Res. Mol. Biol., 2000, 64, 221-253.
[http://dx.doi.org/10.1016/S0079-6603(00)64006-0]
[69]
Boritzki, T.J.; Wolfard, T.S.; Besserer, J.A.; Jackson, R.C.; Fry, D.W. Inhibition of type II topoisomerase by fostriecin. Biochem. Pharmacol., 1988, 37(21), 4063-4068.
[http://dx.doi.org/10.1016/0006-2952(88)90096-2] [PMID: 2847752]
[70]
Wall, M.E.; Wani, M.C. Camptothecin and taxol: discovery to clinic--thirteenth Bruce F. Cain memorial award lecture. Cancer Res., 1995, 55(4), 753-760.
[PMID: 7850785]
[71]
Pommier, Y. Drugging topoisomerases: lessons and challenges. ACS Chem. Biol., 2013, 8(1), 82-95.
[http://dx.doi.org/10.1021/cb300648v] [PMID: 23259582]
[72]
Pommier, Y. Topoisomerase I inhibitors: camptothecins and beyond. Nat. Rev. Cancer, 2006, 6(10), 789-802.
[http://dx.doi.org/10.1038/nrc1977] [PMID: 16990856]
[73]
Cheng, Y.; An, L-K.; Wu, N.; Wang, X-D.; Bu, X-Z.; Huang, Z-S.; Gu, L.Q. Synthesis, cytotoxic activities and structure-activity relationships of topoisomerase I inhibitors: indolizinoquinoline-5,12-dione derivatives. Bioorg. Med. Chem., 2008, 16(8), 4617-4625.
[http://dx.doi.org/10.1016/j.bmc.2008.02.036] [PMID: 18296054]
[74]
Suh, M-E.; Kang, M-J.; Park, S-Y. The 3-D QSAR study of anticancer 1-N-substituted imidazo- and pyrrolo-quinoline-4,9-dione derivatives by CoMFA and CoMSIA. Bioorg. Med. Chem., 2001, 9(11), 2987-2991.
[http://dx.doi.org/10.1016/S0968-0896(01)00196-1] [PMID: 11597480]
[75]
Shaikh, I.A.; Johnson, F.; Grollman, A.P. Streptonigrin. 1. Structure-activity relationships among simple bicyclic analogues. Rate dependence of DNA degradation on quinone reduction potential. J. Med. Chem., 1986, 29(8), 1329-1340.
[http://dx.doi.org/10.1021/jm00158a002] [PMID: 3525839]
[76]
Park, H.J.; Lee, H-J.; Lee, E-J.; Hwang, H.J.; Shin, S-H. Cytotoxicity and DNA topoisomerase inhibitory activity of benz [f] indole-4, 9-dione analogs. Biosci. Biotechnol. Biochem., 2003, 67, 1944-1949.
[77]
Moore, M.H.; Hunter, W.N.; d’Estaintot, B.L.; Kennard, O. DNA-drug interactions. The crystal structure of d(CGATCG) complexed with daunomycin. J. Mol. Biol., 1989, 206(4), 693-705.
[http://dx.doi.org/10.1016/0022-2836(89)90577-9] [PMID: 2738914]
[78]
Fan, E.; Shi, W.; Lowary, T.L. Synthesis of daunorubicin analogues containing truncated aromatic cores and unnatural monosaccharide residues. J. Org. Chem., 2007, 72(8), 2917-2928.
[http://dx.doi.org/10.1021/jo062542q] [PMID: 17373847]
[79]
Minotti, G.; Menna, P.; Salvatorelli, E.; Cairo, G.; Gianni, L. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol. Rev., 2004, 56(2), 185-229.
[http://dx.doi.org/10.1124/pr.56.2.6] [PMID: 15169927]
[80]
Qu, X.; Wan, C.; Becker, H-C.; Zhong, D.; Zewail, A.H. The anticancer drug-DNA complex: femtosecond primary dynamics for anthracycline antibiotics function. Proc. Natl. Acad. Sci. USA, 2001, 98(25), 14212-14217.
[http://dx.doi.org/10.1073/pnas.241509698] [PMID: 11724924]
[81]
Wang, A.H.; Ughetto, G.; Quigley, G.J.; Rich, A. Interactions between an anthracycline antibiotic and DNA: molecular structure of daunomycin complexed to d(CpGpTpApCpG) at 1.2-A resolution. Biochemistry, 1987, 26(4), 1152-1163.
[http://dx.doi.org/10.1021/bi00378a025] [PMID: 3567161]
[82]
Shi, W.; Coleman, R.S.; Lowary, T.L. Synthesis and DNA-binding affinity studies of glycosylated intercalators designed as functional mimics of the anthracycline antibiotics. Org. Biomol. Chem., 2009, 7(18), 3709-3722.
[http://dx.doi.org/10.1039/b909153j] [PMID: 19707675]
[83]
Shi, W.; Marcus, S.L.; Lowary, T.L. Cytotoxicity and topoisomerase I/II inhibition of glycosylated 2-phenyl-indoles, 2-phenyl-benzo[b]thiophenes and 2-phenyl-benzo[b]furans. Bioorg. Med. Chem., 2011, 19(1), 603-612.
[http://dx.doi.org/10.1016/j.bmc.2010.10.054] [PMID: 21094049]
[84]
Bifulco, G.; Bruno, I.; Minale, L.; Riccio, R.; Calignano, A.; Debitus, C. (+/-)-Gelliusines A and B, two diastereomeric brominated tris-indole alkaloids from a deep water new caledonian marine sponge (Gellius or Orina sp.). J. Nat. Prod., 1994, 57(9), 1294-1299.
[http://dx.doi.org/10.1021/np50111a020] [PMID: 7798965]
[85]
Chao, W-R.; Yean, D.; Amin, K.; Green, C.; Jong, L. Computer-aided rational drug design: a novel agent (SR13668) designed to mimic the unique anticancer mechanisms of dietary indole-3-carbinol to block Akt signaling. J. Med. Chem., 2007, 50(15), 3412-3415.
[http://dx.doi.org/10.1021/jm070040e] [PMID: 17602463]
[86]
Kusurkar, R.S.; Goswami, S.K.; Vyas, S.M. Efficient one-pot synthesis of anti HIV and antitumor compounds: harman and substituted harmans. Tetrahedron Lett., 2003, 44, 4761-4763.
[http://dx.doi.org/10.1016/S0040-4039(03)01046-3]
[87]
Barsanti, P.A.; Wang, W.; Ni, Z-J.; Duhl, D.; Brammeier, N.; Martin, E.; Bussiere, D.; Walter, A.O. The discovery of tetrahydro-β-carbolines as inhibitors of the kinesin Eg5. Bioorg. Med. Chem. Lett., 2010, 20(1), 157-160.
[http://dx.doi.org/10.1016/j.bmcl.2009.11.012] [PMID: 19945875]
[88]
Kumar, R.; Gupta, L.; Pal, P.; Khan, S.; Singh, N.; Katiyar, S.B.; Meena, S.; Sarkar, J.; Sinha, S.; Kanaujiya, J.K.; Lochab, S.; Trivedi, A.K.; Chauhan, P.M. Synthesis and cytotoxicity evaluation of (tetrahydro-β-carboline)-1,3,5-triazine hybrids as anticancer agents. Eur. J. Med. Chem., 2010, 45(6), 2265-2276.
[http://dx.doi.org/10.1016/j.ejmech.2010.02.001] [PMID: 20207053]
[89]
Tonin, L.T.D.; Barbosa, V.A.; Bocca, C.C.; Ramos, É.R.; Nakamura, C.V.; da Costa, W.F.; Basso, E.A.; Nakamura, T.U.; Sarragiotto, M.H. Comparative study of the trypanocidal activity of the methyl 1-nitrophenyl-1,2,3,4-9H-tetrahydro-β-carboline-3-carboxylate derivatives and benznidazole using theoretical calculations and cyclic voltammetry. Eur. J. Med. Chem., 2009, 44(4), 1745-1750.
[http://dx.doi.org/10.1016/j.ejmech.2008.03.044] [PMID: 18504061]
[90]
Beljanski, M.; Beljanski, M.S. Selective inhibition of in vitro synthesis of cancer DNA by alkaloids of β-carboline class. Exp. Cell Biol., 1982, 50(2), 79-87.
[PMID: 7075859]
[91]
Sobhani, A.M.; Ebrahimi, S-A.; Mahmoudian, M. An in vitro evaluation of human DNA topoisomerase I inhibition by Peganum harmala L. seeds extract and its beta-carboline alkaloids. J. Pharm. Pharm. Sci., 2002, 5(1), 19-23.
[PMID: 12042115]
[92]
Deveau, A.M.; Labroli, M.A.; Dieckhaus, C.M.; Barthen, M.T.; Smith, K.S.; Macdonald, T.L. The synthesis of amino-acid functionalized β-carbolines as topoisomerase II inhibitors. Bioorg. Med. Chem. Lett., 2001, 11(10), 1251-1255.
[http://dx.doi.org/10.1016/S0960-894X(01)00136-6] [PMID: 11392530]
[93]
Anderson, W.K.; Halat, M.J. Antileukemic activity of derivatives of 1,2-dimethyl-3,4-bis(hydroxymethyl)-5-phenylpyrrole bis(N-methylcarbamate). J. Med. Chem., 1979, 22(8), 977-980.
[http://dx.doi.org/10.1021/jm00194a018] [PMID: 490542]
[94]
Staker, B.L.; Feese, M.D.; Cushman, M.; Pommier, Y.; Zembower, D.; Stewart, L.; Burgin, A.B. Structures of three classes of anticancer agents bound to the human topoisomerase I-DNA covalent complex. J. Med. Chem., 2005, 48(7), 2336-2345.
[http://dx.doi.org/10.1021/jm049146p] [PMID: 15801827]
[95]
Wang, J-C.; Lin, J-H.; Chen, C-M.; Perryman, A.L.; Olson, A.J. Robust scoring functions for protein-ligand interactions with quantum chemical charge models. J. Chem. Inf. Model., 2011, 51(10), 2528-2537.
[http://dx.doi.org/10.1021/ci200220v] [PMID: 21932857]
[96]
Chaniyara, R.; Tala, S.; Chen, C-W.; Zang, X.; Kakadiya, R.; Lin, L-F.; Chen, C.H.; Chien, S.I.; Chou, T.C.; Tsai, T.H.; Lee, T.C.; Shah, A.; Su, T.L. Novel antitumor indolizino [6,7-b]indoles with multiple modes of action: DNA cross-linking and topoisomerase I and II inhibition. J. Med. Chem., 2013, 56(4), 1544-1563.
[http://dx.doi.org/10.1021/jm301788a] [PMID: 23360284]
[97]
Chen, C-W.; Wu, M-H.; Chen, Y-F.; Yen, T-Y.; Lin, Y-W.; Chao, S-H.; Tala, S.; Tsai, T.H.; Su, T.L.; Lee, T.C. A potent derivative of indolizino [6, 7-b] indole for treatment of human non–small cell lung cancer cells. Neoplasia, 2016, 18(4), 199-212.
[http://dx.doi.org/10.1016/j.neo.2016.02.005] [PMID: 27108383]
[98]
Gallinari, P.; Di Marco, S.; Jones, P.; Pallaoro, M.; Steinkühler, C. HDACs, histone deacetylation and gene transcription: from molecular biology to cancer therapeutics. Cell Res., 2007, 17(3), 195-211.
[http://dx.doi.org/10.1038/sj.cr.7310149] [PMID: 17325692]
[99]
Witt, O.; Deubzer, H.E.; Milde, T.; Oehme, I. HDAC family: what are the cancer relevant targets? Cancer Lett., 2009, 277(1), 8-21.
[http://dx.doi.org/10.1016/j.canlet.2008.08.016] [PMID: 18824292]
[100]
Marks, P.A. Discovery and development of SAHA as an anticancer agent. Oncogene, 2007, 26(9), 1351-1356.
[http://dx.doi.org/10.1038/sj.onc.1210204] [PMID: 17322921]
[101]
Furlan, A.; Monzani, V.; Reznikov, L.L.; Leoni, F.; Fossati, G.; Modena, D.; Mascagni, P.; Dinarello, C.A. Pharmacokinetics, safety and inducible cytokine responses during a phase 1 trial of the oral histone deacetylase inhibitor ITF2357 (givinostat). Mol. Med., 2011, 17(5-6), 353-362.
[http://dx.doi.org/10.2119/molmed.2011.00020] [PMID: 21365126]
[102]
Fouliard, S.; Robert, R.; Jacquet-Bescond, A.; du Rieu, Q.C.; Balasubramanian, S.; Loury, D.; Loriot, Y.; Hollebecque, A.; Kloos, I.; Soria, J.C.; Chenel, M.; Depil, S. Pharmacokinetic/pharmacodynamic modelling-based optimisation of administration schedule for the histone deacetylase inhibitor abexinostat (S78454/PCI-24781) in phase I. Eur. J. Cancer, 2013, 49(13), 2791-2797.
[http://dx.doi.org/10.1016/j.ejca.2013.05.009] [PMID: 23790467]
[103]
Plumb, J.A.; Finn, P.W.; Williams, R.J.; Bandara, M.J.; Romero, M.R.; Watkins, C.J.; La Thangue, N.B.; Brown, R. Pharmacodynamic response and inhibition of growth of human tumor xenografts by the novel histone deacetylase inhibitor PXD101. Mol. Cancer Ther., 2003, 2(8), 721-728.
[PMID: 12939461]
[104]
Novotny-Diermayr, V.; Sangthongpitag, K.; Hu, C.Y.; Wu, X.; Sausgruber, N.; Yeo, P.; Greicius, G.; Pettersson, S.; Liang, A.L.; Loh, Y.K.; Bonday, Z.; Goh, K.C.; Hentze, H.; Hart, S.; Wang, H.; Ethirajulu, K.; Wood, J.M. SB939, a novel potent and orally active histone deacetylase inhibitor with high tumor exposure and efficacy in mouse models of colorectal cancer. Mol. Cancer Ther., 2010, 9(3), 642-652.
[http://dx.doi.org/10.1158/1535-7163.MCT-09-0689] [PMID: 20197387]
[105]
Wang, H.; Yu, N.; Chen, D.; Lee, K.C.L.; Lye, P.L.; Chang, J.W.W.; Deng, W.; Ng, M.C.; Lu, T.; Khoo, M.L.; Poulsen, A.; Sangthongpitag, K.; Wu, X.; Hu, C.; Goh, K.C.; Wang, X.; Fang, L.; Goh, K.L.; Khng, H.H.; Goh, S.K.; Yeo, P.; Liu, X.; Bonday, Z.; Wood, J.M.; Dymock, B.W.; Kantharaj, E.; Sun, E.T. Discovery of (2E)-3-2-butyl-1-[2-(diethylamino)ethyl]-1H-benzimidazol-5-yl-N-hydroxyacrylamide (SB939), an orally active histone deacetylase inhibitor with a superior preclinical profile. J. Med. Chem., 2011, 54(13), 4694-4720.
[http://dx.doi.org/10.1021/jm2003552] [PMID: 21634430]
[106]
de Bono, J.S.; Kristeleit, R.; Tolcher, A.; Fong, P.; Pacey, S.; Karavasilis, V.; Mita, M.; Shaw, H.; Workman, P.; Kaye, S.; Rowinsky, E.K.; Aherne, W.; Atadja, P.; Scott, J.W.; Patnaik, A. Phase I pharmacokinetic and pharmacodynamic study of LAQ824, a hydroxamate histone deacetylase inhibitor with a heat shock protein-90 inhibitory profile, in patients with advanced solid tumors. Clin. Cancer Res., 2008, 14(20), 6663-6673.
[http://dx.doi.org/10.1158/1078-0432.CCR-08-0376] [PMID: 18927309]
[107]
Atadja, P. Development of the pan-DAC inhibitor panobinostat (LBH589): successes and challenges. Cancer Lett., 2009, 280(2), 233-241.
[http://dx.doi.org/10.1016/j.canlet.2009.02.019] [PMID: 19344997]
[108]
Dai, Y.; Guo, Y.; Guo, J.; Pease, L.J.; Li, J.; Marcotte, P.A.; Glaser, K.B.; Tapang, P.; Albert, D.H.; Richardson, P.L.; Davidsen, S.K.; Michaelides, M.R. Indole amide hydroxamic acids as potent inhibitors of histone deacetylases. Bioorg. Med. Chem. Lett., 2003, 13(11), 1897-1901.
[http://dx.doi.org/10.1016/S0960-894X(03)00301-9] [PMID: 12749893]
[109]
Giannini, G.; Marzi, M.; Marzo, M.D.; Battistuzzi, G.; Pezzi, R.; Brunetti, T.; Cabri, W.; Vesci, L.; Pisano, C. Exploring bis-(indolyl)methane moiety as an alternative and innovative CAP group in the design of histone deacetylase (HDAC) inhibitors. Bioorg. Med. Chem. Lett., 2009, 19(10), 2840-2843.
[http://dx.doi.org/10.1016/j.bmcl.2009.03.101] [PMID: 19359173]
[110]
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.
[http://dx.doi.org/10.1021/ml300366t] [PMID: 23493449]
[111]
Li, X.; Inks, E.S.; Li, X.; Hou, J.; Chou, C.J.; Zhang, J.; Jiang, Y.; Zhang, Y.; Xu, W. Discovery of the first N-hydroxycinnamamide-based histone deacetylase 1/3 dual inhibitors with potent oral antitumor activity. J. Med. Chem., 2014, 57(8), 3324-3341.
[http://dx.doi.org/10.1021/jm401877m] [PMID: 24694055]
[112]
Jiao, J.; Fang, H.; Wang, X.; Guan, P.; Yuan, Y.; Xu, W. Design, synthesis and preliminary biological evaluation of N-hydroxy-4-(3-phenylpropan-amido)benzamide (HPPB) derivatives as novel histone deacetylase inhibitors. Eur. J. Med. Chem., 2009, 44(11), 4470-4476.
[http://dx.doi.org/10.1016/j.ejmech.2009.06.010] [PMID: 19608304]
[113]
Zhang, L.; Wang, X.; Li, X.; Xu, W. Discovery of a series of small molecules as potent histone deacetylase inhibitors. J. Enzyme Inhib. Med. Chem., 2014, 29(3), 333-337.
[http://dx.doi.org/10.3109/14756366.2013.780237] [PMID: 23534931]
[114]
Li, X.; Wu, J.; Li, X.; Mu, W.; Liu, X.; Jin, Y.; Xu, W.; Zhang, Y. Development of N-hydroxybenzamide derivatives with indole-containing cap group as histone deacetylases inhibitors. Bioorg. Med. Chem., 2015, 23(19), 6258-6270.
[http://dx.doi.org/10.1016/j.bmc.2015.08.040] [PMID: 26349626]
[115]
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.
[http://dx.doi.org/10.1111/cbdd.12819] [PMID: 27416889]
[116]
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.
[http://dx.doi.org/10.1021/jm0703136] [PMID: 17691763]
[117]
Lai, M-J.; Huang, H-L.; Pan, S-L.; Liu, Y-M.; Peng, C-Y.; Lee, H-Y.; Yeh, T.K.; Huang, P.H.; Teng, C.M.; Chen, C.S.; Chuang, H.Y.; Liou, J.P. Synthesis and biological evaluation of 1-arylsulfonyl-5-(N-hydroxyacrylamide)-indoles as potent histone deacetylase inhibitors with antitumor activity in vivo. J. Med. Chem., 2012, 55(8), 3777-3791.
[http://dx.doi.org/10.1021/jm300197a] [PMID: 22439863]
[118]
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-ethylsulfamoyl-phenylacrylamides: potent histone deacetylase inhibitors with anti-inflammatory activity. Eur. J. Med. Chem., 2014, 85, 468-479.
[http://dx.doi.org/10.1016/j.ejmech.2014.08.020] [PMID: 25113875]
[119]
Cai, M.; Hu, J.; Tian, J-L.; Yan, H.; Zheng, C-G.; Hu, W-L. Novel hybrids from N-hydroxyarylamide and indole ring through click chemistry as histone deacetylase inhibitors with potent antitumor activities. Chin. Chem. Lett., 2015, 26, 675-680.
[http://dx.doi.org/10.1016/j.cclet.2015.03.015]
[120]
Krennhrubec, K.; Marshall, B.L.; Hedglin, M.; Verdin, E.; Ulrich, S.M. Design and evaluation of ‘Linkerless’ hydroxamic acids as selective HDAC8 inhibitors. Bioorg. Med. Chem. Lett., 2007, 17(10), 2874-2878.
[http://dx.doi.org/10.1016/j.bmcl.2007.02.064] [PMID: 17346959]