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ISSN (Online): 1875-628X

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Review Article

Anticancer Tetrahydrocarbazoles: A Wide Journey from 2000 Till Date

Author(s): Nitin Kumar* and Pankaj Gupta

Volume 21, Issue 3, 2024

Published on: 16 November, 2022

Page: [421 - 439] Pages: 19

DOI: 10.2174/1570180820666221028163319

Price: $65

Abstract

Tetrahydrocarbazoles (THCz) are widespread in numerous indole alkaloids and have been reported since time for exhibiting profound pharmacological potential. Many pharmaceuticals drugs have tetrahydrocarbazole nucleus in their structure e.g. vinca alkaloids (Vincristine, Vinblastine, Vinorelbine), Frovatriptan, (R)-Ramatroban, Ondansetron, etc. that are used in various multifactorial diseases. In this review article, the anticancer potential of tetrahydrocarbazole based derivatives has been covered, enumerating their vast journey from the year 2000 to 2021. Since the last twenty-one years, tetrahydrocarbazoles have been a matter of focus among researchers worldwide, whereby several novel tetrahydrocarbazole derivatives have been synthesized and reported for their anticancer potential against various cancer cell lines. Tetrahydrocarabzole and its derivatives have exhibited profound anticancer potential mediated via various cancer pathways like apoptosis, cell cycle arrest, microtubule inhibition, Nrf2 Modulators, DNA intercalators, pERK and pRb phosphorylation, VEGF (Vascular Endothelial Growth Factor) and TNF-α inhibition, TPSO (translocator protein), Histone Deacetylase (HDAC) Inhibitors also discussed. The present review entails the synthesis, SAR studies, and anticancer mechanism of tetrahydrocarbazoles derivatives reported in review literature till date, and would provide a strong database to the medicinal chemist world over in discovering newer potential anticancer agent against various types of cancer diseases.

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[1]
WHO report on cancer: Setting priorities, investing wisely and providing care for all World Health organization. WHO Organization, 2020.
[2]
World Health Organization (WHO). Global Health Estimates 2020: Deaths by Cause, Age, Sex, by Country and by Region, 2000-2019., 2020.
[3]
Wellington, K.W. Understanding cancer and the anticancer activities of naphthoquinones – a review. RSC Advances, 2015, 5(26), 20309-20338.
[http://dx.doi.org/10.1039/C4RA13547D]
[4]
Kumar, N.; Lal, N.; Nemaysh, V.; Luthra, P.M. Design, synthesis, DNA binding studies and evaluation of anticancer potential of novel substituted biscarbazole derivatives against human glioma U87 MG cell line. Bioorg. Chem., 2020, 100, 103911.
[http://dx.doi.org/10.1016/j.bioorg.2020.103911] [PMID: 32502918]
[5]
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[6]
Mathur, P.; Sathishkumar, K.; Chaturvedi, M.; Das, P.; Sudarshan, K.L.; Santhappan, S.; Nallasamy, V.; John, A.; Narasimhan, S.; Roselind, F.S. Cancer statistics, 2020: Report from national cancer registry programme, India. JCO Glob. Oncol., 2020, 6(6), 1063-1075.
[http://dx.doi.org/10.1200/GO.20.00122] [PMID: 32673076]
[7]
Kumar, N.; Kumar, R.; Nemaysh, V.; Lal, N.; Luthra, P.M. Bis((1,4-dimethyl-9H-carbazol-3-yl)methyl)amine-mediated anticancer effect triggered by sequence-specific cleavage of DNA leading to programmed cell death in the human U87 cell line. RSC Advances, 2016, 6(72), 67925-67940.
[http://dx.doi.org/10.1039/C6RA12999D]
[8]
Kulkarni, M.R.; Mane, M.S.; Ghosh, U.; Sharma, R.; Lad, N.P.; Srivastava, A.; Kulkarni-Almeida, A.; Kharkar, P.S.; Khedkar, V.M.; Pandit, S.S. Discovery of tetrahydrocarbazoles as dual pERK and pRb inhibitors. Eur. J. Med. Chem., 2017, 134, 366-378.
[http://dx.doi.org/10.1016/j.ejmech.2017.02.062] [PMID: 28431342]
[9]
Housman, G.; Byler, S.; Heerboth, S.; Lapinska, K.; Longacre, M.; Snyder, N.; Sarkar, S. Drug resistance in cancer: An overview. Cancers (Basel), 2014, 6(3), 1769-1792.
[http://dx.doi.org/10.3390/cancers6031769] [PMID: 25198391]
[10]
Luthra, P.M.; Kumar, N. Progress and development of C-3, C-6, and N-9 positions substituted carbazole integrated molecular hybrid molecules as potential anticancer agents. Mini Rev. Med. Chem., 2021, 21(19), 2929-2956.
[http://dx.doi.org/10.2174/1389557521666210521221808] [PMID: 34036916]
[11]
Kumar, N.; Kumar, V.; Chaudhary, Y. A review on synthesis methods of tricyclic 1,2,3,4-tetrahydrocarbazoles. World J. Adv. Res. Rev., 2022, 13(01), 160-171.
[12]
Dhanalakshmi, G.; Saravanan, V.; Mohanakrishnan, A.K.; Aravindhan, S. Synthesis, crystal structure, hirshfeld surface, energy framework and molecular docking analysis of two novel carbazole derivatives. Asian J. Chem., 2019, 31(12), 3017-3028.
[http://dx.doi.org/10.14233/ajchem.2019.22430]
[13]
Padmavathi, S.; Tajne, M.R. Design, synthesis, molecular docking studies and anti-microbial activity of novel 1,2,3,4-tetrahydrocarbazole derivatives. Int. Curr. Pharm. J., 2016, 5(9), 73-78.
[http://dx.doi.org/10.3329/icpj.v5i9.29231]
[14]
Singh, M.; Sharma, P.; Arora, S. Development of 1,2,3,4‐tetrahydrocarbazole derivatives as dual binding cholinestarse inhibitors. Alzheimers Dement., 2021, 17(S9), e051020.
[http://dx.doi.org/10.1002/alz.051020]
[15]
Wang, W.; Dong, G.; Gu, J.; Zhang, Y.; Wang, S.; Zhu, S.; Liu, Y.; Miao, Z.; Yao, J.; Zhang, W.; Sheng, C. Structure–activity relationships of tetrahydrocarbazole derivatives as antifungal lead compounds. MedChemComm, 2013, 4(2), 353-362.
[http://dx.doi.org/10.1039/C2MD20211E]
[16]
Wang, L.L.; Du, Y.; Li, S.M.; Cheng, F.; Zhang, N.N.; Chen, R.; Cui, X.; Yang, S.G.; Fan, L.L.; Wang, J.T.; Guo, B.; Wu, H.S.; Zhang, J.Q.; Tang, L. Design, synthesis and evaluation of tetrahydrocarbazole derivatives as potential hypoglycemic agents. Bioorg. Chem., 2021, 115, 105172.
[http://dx.doi.org/10.1016/j.bioorg.2021.105172] [PMID: 34303898]
[17]
Chakroborty, S.; Panda, P. A comprehensive overview of the synthesis of tetrahydrocarbazoles and its biological properties. Mini Rev. Org. Chem., 2021, 18(6), 709-718.
[http://dx.doi.org/10.2174/1570193X17999200820163532]
[18]
Al-Mohson, A.; Mohammed, Z. Synthesis of novel pyrazole derivatives containing tetrahydrocarbazole, antimicrobial evaluation and molecular properties. Eur. Chem. Commun., 2021, 3(6), 425-434.
[19]
Sakinala, P.; Chikhale, R.; Tajne, M. Design, synthesis and pharmacological evaluation of some novel tetrahydrocarbazoles as potential COX-2 inhibitors. Lett. Drug Des. Discov., 2018, 15(4), 437-449.
[http://dx.doi.org/10.2174/1570180814666170602084037]
[20]
El-Nassan, H.B. Synthesis and antitumor activity of tetrahydrocarbazole hybridized with dithioate derivatives. J. Enzyme Inhib. Med. Chem., 2015, 30(2), 308-315.
[http://dx.doi.org/10.3109/14756366.2014.922554] [PMID: 24899376]
[21]
Ghobadian, R.; Mahdavi, M.; Nadri, H.; Moradi, A.; Edraki, N.; Akbarzadeh, T.; Sharifzadeh, M.; Bukhari, S.N.A.; Amini, M. Novel tetrahydrocarbazole benzyl pyridine hybrids as potent and selective butryl cholinesterase inhibitors with neuroprotective and β-secretase inhibition activities. Eur. J. Med. Chem., 2018, 155, 49-60.
[http://dx.doi.org/10.1016/j.ejmech.2018.05.031] [PMID: 29857276]
[22]
Harvey, R.; Brown, K.; Zhang, Q.; Gartland, M.; Walton, L.; Talarico, C.; Lawrence, W.; Selleseth, D.; Coffield, N.; Leary, J.; Moniri, K.; Singer, S.; Strum, J.; Gudmundsson, K.; Biron, K.; Romines, K.R.; Sethna, P. GSK983: A novel compound with broad-spectrum antiviral activity. Antiviral Res., 2009, 82(1), 1-11.
[http://dx.doi.org/10.1016/j.antiviral.2008.12.015] [PMID: 19187793]
[23]
Caruso, A.; Ceramella, J.; Iacopetta, D.; Saturnino, C.; Mauro, M.V.; Bruno, R.; Aquaro, S.; Sinicropi, M.S. Carbazole derivatives as antiviral agents: An overview. Molecules, 2019, 24(10), 1912.
[http://dx.doi.org/10.3390/molecules24101912] [PMID: 31109016]
[24]
Lang, D.K.; Kaur, R.; Arora, R.; Saini, B.; Arora, S. Nitrogen-containing heterocycles as anticancer agents: An overview. Anticancer. Agents Med. Chem., 2020, 20(18), 2150-2168.
[25]
Kerru, N.; Gummidi, L.; Maddila, S.; Gangu, K.K.; Jonnalagadda, S.B. A review on recent advances in nitrogen-containing molecules and their biological applications. Molecules, 2020, 25(8), 1909.
[http://dx.doi.org/10.3390/molecules25081909] [PMID: 32326131]
[26]
Heravi, M.M.; Amiri, Z.; Kafshdarzadeh, K.; Zadsirjan, V. Synthesis of indole derivatives as prevalent moieties present in selected alkaloids. RSC Advances, 2021, 11(53), 33540-33612.
[http://dx.doi.org/10.1039/D1RA05972F] [PMID: 35497516]
[27]
Song, F.; Liu, D.; Huo, X.; Qiu, D. The anticancer activity of carbazole alkaloids. Arch. Pharm. (Weinheim), 2022, 355(1), 2100277.
[http://dx.doi.org/10.1002/ardp.202100277] [PMID: 34486161]
[28]
Tan, F.; Cheng, H.G. Catalytic asymmetric synthesis of tetrahydrocarbazoles. Chem. Commun. (Camb.), 2019, 55(44), 6151-6164.
[http://dx.doi.org/10.1039/C9CC02486G] [PMID: 31093637]
[29]
Kumar, S. Ritika, A brief review of the biological potential of indole derivatives. Fut. J. Pharm. Sci., 2020, 6(1), 121.
[http://dx.doi.org/10.1186/s43094-020-00141-y]
[30]
Issa, S.; Prandina, A.; Bedel, N.; Rongved, P.; Yous, S.; Le Borgne, M.; Bouaziz, Z. Carbazole scaffolds in cancer therapy: A review from 2012 to 2018. J. Enzyme Inhib. Med. Chem., 2019, 34(1), 1321-1346.
[http://dx.doi.org/10.1080/14756366.2019.1640692] [PMID: 31328585]
[31]
Kumar, N.; Kumar Singh, K.; Mehta Luthra, P. A review on anticancer potential of some pyranocarbazole alkaloids and its derivatives. Int. J. Adv. Res. (Indore), 2021, 9(6), 874-883.
[http://dx.doi.org/10.21474/IJAR01/13091]
[32]
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]
[33]
Samanta, S.K.; Kandimalla, R.; Gogoi, B.; Dutta, K.N.; Choudhury, P.; Deb, P.K.; Devi, R.; Pal, B.C.; Talukdar, N.C. Phytochemical portfolio and anticancer activity of Murraya koenigii and its primary active component, mahanine. Pharmacol. Res., 2018, 129, 227-236.
[http://dx.doi.org/10.1016/j.phrs.2017.11.024] [PMID: 29175114]
[34]
Astaneh, M.; Ghafouri-Fard, S.; Fazeli, Z.; Taherian-Esfahani, Z.; Dashti, S.; Motevaseli, E. Assessment of anti-cancer effects of koenimbine on colon cancer cells. Hum. Antibodies, 2020, 28(3), 185-190.
[http://dx.doi.org/10.3233/HAB-200405] [PMID: 32116245]
[35]
Patel, O.P.S.; Arun, A.; Singh, P.K.; Saini, D.; Karade, S.S.; Chourasia, M.K.; Konwar, R.; Yadav, P.P. Pyranocarbazole derivatives as potent anti-cancer agents triggering tubulin polymerization stabilization induced activation of caspase-dependent apoptosis and downregulation of Akt/mTOR in breast cancer cells. Eur. J. Med. Chem., 2019, 167, 226-244.
[http://dx.doi.org/10.1016/j.ejmech.2019.02.003] [PMID: 30772606]
[36]
Arun, A.; Patel, O.P.S.; Saini, D.; Yadav, P.P.; Konwar, R. Anti-colon cancer activity of Murraya koenigii leaves is due to constituent murrayazoline and O-methylmurrayamine A induced mTOR/AKT downregulation and mitochondrial apoptosis. Biomed. Pharmacother., 2017, 93, 510-521.
[http://dx.doi.org/10.1016/j.biopha.2017.06.065] [PMID: 28675857]
[37]
Syam, S.; Abdul, A.B.; Sukari, M.A.; Mohan, S.; Abdelwahab, S.I.; Wah, T.S. The growth suppressing effects of girinimbine on HepG2 involve induction of apoptosis and cell cycle arrest. Molecules, 2011, 16(8), 7155-7170.
[http://dx.doi.org/10.3390/molecules16087155] [PMID: 21862957]
[38]
Yang, L.; Yu, X. Naturally occurring Girinimbine alkaloid inhibits the proliferation, migration, and invasion of human breast cancer cells via induction of apoptosis and inhibition of MEK/ERK and STAT3 signalling pathways. Acta Biochim. Pol., 2021, 68(4), 647-652.
[http://dx.doi.org/10.18388/abp.2020_5531] [PMID: 34472799]
[39]
Itoigawa, M.; Kashiwada, Y.; Ito, C.; Furukawa, H.; Tachibana, Y.; Bastow, K.F.; Lee, K.H. Antitumor agents. 203. Carbazole alkaloid murrayaquinone A and related synthetic carbazolequinones as cytotoxic agents. J. Nat. Prod., 2000, 63(7), 893-897.
[http://dx.doi.org/10.1021/np000020e] [PMID: 10924160]
[40]
Maruthanila, V.L.; Elancheran, R.; Kunnumakkar, A.B.; Kabilan, S. Kotoky, J Pleiotropic Effect of mahanine and girinimbine analogs: Anticancer mechanism and its therapeutic versatility. Anticancer. Agents Med. Chem., 2018, 18(14), 1983-1990.
[41]
Garbett, N.; Graves, D. Extending nature’s leads: The anticancer agent ellipticine. Curr. Med. Chem. Anticancer Agents, 2004, 4(2), 149-172.
[http://dx.doi.org/10.2174/1568011043482070] [PMID: 15032720]
[42]
Caruso, A.; Iacopetta, D.; Puoci, F.; Rita Cappello, A.; Saturnino, C.; Stefania Sinicropi, M. Carbazole derivatives: A promising scenario for breast cancer treatment. Mini Rev. Med. Chem., 2016, 16(8), 630-643.
[http://dx.doi.org/10.2174/1389557515666150709111342] [PMID: 26156543]
[43]
Caruso, A.; Sinicropi, M.S.; Lancelot, J.C.; El-Kashef, H.; Saturnino, C.; Aubert, G.; Ballandonne, C.; Lesnard, A.; Cresteil, T.; Dallemagne, P.; Rault, S. Synthesis and evaluation of cytotoxic activities of new guanidines derived from carbazoles. Bioorg. Med. Chem. Lett., 2014, 24(2), 467-472.
[http://dx.doi.org/10.1016/j.bmcl.2013.12.047] [PMID: 24374274]
[44]
Vairavelu, L.; Zeller, M.; Rajendra Prasad, K.J. Solvent-free synthesis of heteroannulated carbazoles: A novel class of anti-tumor agents. Bioorg. Chem., 2014, 54, 12-20.
[http://dx.doi.org/10.1016/j.bioorg.2014.03.003] [PMID: 24698746]
[45]
Chaudhari, T.Y.; Tandon, V. Recent approaches to the synthesis of tetrahydrocarbazoles. Org. Biomol. Chem., 2021, 19(9), 1926-1939.
[http://dx.doi.org/10.1039/D0OB02274H] [PMID: 33570535]
[46]
Keglevich, P.; Hazai, L.; Kalaus, G.; Szántay, C. Modifications on the basic skeletons of vinblastine and vincristine. Molecules, 2012, 17(5), 5893-5914.
[http://dx.doi.org/10.3390/molecules17055893] [PMID: 22609781]
[47]
Easthope, S.E.; Goa, K.L. Frovatriptan. CNS Drugs, 2001, 15(12), 969-976.
[http://dx.doi.org/10.2165/00023210-200115120-00006] [PMID: 11735616]
[48]
Ishizuka, T.; Matsui, T.; Okamoto, Y.; Ohta, A.; Shichijo, M. Ramatroban (BAY u 3405): A novel dual antagonist of TXA2 receptor and CRTh2, a newly identified prostaglandin D2 receptor. Cardiovasc. Drug Rev., 2004, 22(2), 71-90.
[http://dx.doi.org/10.1111/j.1527-3466.2004.tb00132.x] [PMID: 15179446]
[49]
Cooke, C.E.; Mehra, I.V. Oral ondansetron for preventing nausea and vomiting. Am. J. Health Syst. Pharm., 1994, 51(6), 762-771.
[http://dx.doi.org/10.1093/ajhp/51.6.762] [PMID: 8010314]
[50]
Failli, A.A.; Steffan, R.J.; Kreft, A.F.; Caggiano, T.J.; Caufield, C.E. Pyranoindole and tetrahydrocarbazole inhibitors of COX-2. United States patent US 5,830,911, 1998.
[51]
Deng, W.; Chen, D.; Zhou, Y. Bicyclic heterocycles hydroxamate compounds useful as histone deacetylase (HDAC) inhibitors. PCT Int. Appl., 2006, WO2006101456, 28.
[52]
Marson, CM Histone deacetylase inhibitors: Design, structure-activity relationships and therapeutic implications for cancer. Anticancer. Agents Med. Chem., 2009, 9(6), 661-692.
[http://dx.doi.org/10.2174/187152009788679976]
[53]
Lennox, W.; Qi, H.; Lee, D.H.; Choi, S.; Moon, Y.C. Tetrahydrocarbazoles as active agents for inhibiting VEGF production by translational control. United States patent US 8,946,444, 2015.
[54]
Cao, L.; Weetall, M.; Bombard, J.; Qi, H.; Arasu, T.; Lennox, W.; Hedrick, J.; Sheedy, J.; Risher, N.; Brooks, P.C.; Trifillis, P.; Trotta, C.; Moon, Y.C.; Babiak, J.; Almstead, N.G.; Colacino, J.M.; Davis, T.W.; Peltz, S.W. Discovery of novel small molecule inhibitors of VEGF expression in tumor cells using a cell-based high throughput screening platform. PLoS One, 2016, 11(12), e0168366.
[http://dx.doi.org/10.1371/journal.pone.0168366] [PMID: 27992500]
[55]
Schuster, T.; Paulini, K.; Schmidt, P.; Baasner, S.; Polymeropoulos, E.; Guenther, E.; Teifel, M. Tetrahydrocarbazole derivatives as ligands of G-protein coupled receptors. United States patent US 8,148,546, 2012.
[56]
Paulini, K.; Gerlach, M.; Günther, E.; Polymeropoulos, E.; Baasner, S.; Schmidt, P.; Kühne, R.; Söderhäll, A. Tetrahydrocarbazole derivatives having improved biological action and improved solubility as ligands of G-protein coupled receptors (GPCRs). United States patent US 7,375,127, 2008.
[57]
Lee, Y.T.; Tan, Y.J.; Oon, C.E. Molecular targeted therapy: Treating cancer with specificity. Eur. J. Pharmacol., 2018, 834, 188-196.
[http://dx.doi.org/10.1016/j.ejphar.2018.07.034] [PMID: 30031797]
[58]
Lee, K.Y. M1 and M2 polarization of macrophages: A mini-review. Med. Biol. Sci. Eng., 2019, 2(1), 1-5.
[http://dx.doi.org/10.30579/mbse.2019.2.1.1]
[59]
Grivennikov, S.I.; Greten, F.R.; Karin, M. Immunity, inflammation, and cancer. Cell, 2010, 140(6), 883-899.
[http://dx.doi.org/10.1016/j.cell.2010.01.025] [PMID: 20303878]
[60]
Pei, H.; Qin, J.; Wang, F.; Tan, B.; Zhao, Z.; Peng, Y.; Yu, F.; Li, E.; Liu, M.; Zhang, R.; Liu, B.; Du, B.; Chen, Y. Discovery of potent ureido tetrahydrocarbazole derivatives for cancer treatments through targeting tumor-associated macrophages. Eur. J. Med. Chem., 2019, 183, 111741.
[http://dx.doi.org/10.1016/j.ejmech.2019.111741] [PMID: 31605873]
[61]
Telkoparan-Akillilar, P.; Panieri, E.; Cevik, D.; Suzen, S.; Saso, L. Therapeutic targeting of the NRF2 signaling pathway in cancer. Molecules, 2021, 26(5), 1417.
[http://dx.doi.org/10.3390/molecules26051417] [PMID: 33808001]
[62]
Marengo, B.; Nitti, M.; Furfaro, A.L.; Colla, R.; Ciucis, C.D.; Marinari, U.M.; Pronzato, M.A.; Traverso, N.; Domenicotti, C. Redox homeostasis and cellular antioxidant systems: Crucial players in cancer growth and therapy. Oxid. Med. Cell. Longev., 2016, 6235461.
[http://dx.doi.org/10.1155/2016/6235641]
[63]
Rojo de la Vega, M.; Chapman, E.; Zhang, D.D. NRF2 and the hallmarks of cancer. Cancer Cell, 2018, 34(1), 21-43.
[http://dx.doi.org/10.1016/j.ccell.2018.03.022] [PMID: 29731393]
[64]
Chikkegowda, P.; Pookunoth, B.C.; Bovilla, V.R.; Veeresh, P.M.; Leihang, Z.; Thippeswamy, T.; Padukudru, M.A.; Hathur, B.; Kanchugarakoppal, R.S. Basappa; Madhunapantula, S.V. Design, synthesis, characterization, and crystal structure studies of nrf2 modulators for inhibiting cancer cell growth in vitro and in vivo. ACS Omega, 2021, 6(15), 10054-10071.
[http://dx.doi.org/10.1021/acsomega.0c06345] [PMID: 34056161]
[65]
Mukhtar, E.; Adhami, V.M.; Mukhtar, H. Targeting microtubules by natural agents for cancer therapy. Mol. Cancer Ther., 2014, 13(2), 275-284.
[http://dx.doi.org/10.1158/1535-7163.MCT-13-0791] [PMID: 24435445]
[66]
Schaefer, K.L. PPARγ inhibitors as novel tubulin-targeting agents. PPAR Res., 2008, 2008, 785405.
[67]
Shuai, W.; Wang, G.; Zhang, Y.; Bu, F.; Zhang, S.; Miller, D.D.; Li, W.; Ouyang, L.; Wang, Y. Recent progress on tubulin inhibitors with dual targeting capabilities for cancer therapy. J. Med. Chem., 2021, 64(12), 7963-7990.
[http://dx.doi.org/10.1021/acs.jmedchem.1c00100] [PMID: 34101463]
[68]
Dumontet, C.; Jordan, M.A. Microtubule-binding agents: A dynamic field of cancer therapeutics. Nat. Rev. Drug Discov., 2010, 9(10), 790-803.
[http://dx.doi.org/10.1038/nrd3253] [PMID: 20885410]
[69]
Carmeliet, P. VEGF as a key mediator of angiogenesis in cancer. Oncology, 2005, 69(Suppl. 3), 4-10.
[http://dx.doi.org/10.1159/000088478] [PMID: 16301830]
[70]
Gardner, V.; Madu, C.O.; Lu, Y. Anti-VEGF therapy in cancer: A double-edged sword; Physiol. Pathol. Angiogenesis-Signal. Mech. Targ. Ther, 2017, pp. 385-410.
[http://dx.doi.org/10.5772/66763]
[71]
Wilson, W.D.; Jones, R.L. Intercalating drugs: DNA binding and molecular pharmacology. Adv. Pharmacol., 1981, 18, 177-222.
[http://dx.doi.org/10.1016/S1054-3589(08)60255-0] [PMID: 6172965]
[72]
Kumar, N.; Bansal, S.; Kashyap, S. Kunal. Noncovalent interaction of small molecules by various biophysical techniques and computational approach. World J. Pharm. Res., 2020, 9, 736-747.
[http://dx.doi.org/10.20959/wjpr202012-18861]
[73]
Shmeiss, N.; Ismail, M.; Soliman, A.; El-Diwani, H. Synthesis of novel 1-substituted and 1, 9-disubstituted-1, 2, 3, 4-tetrahydro-9H-carbazole derivatives as potential anticancer agents. Molecules, 2000, 5(12), 1101-1112.
[http://dx.doi.org/10.3390/51001101]
[74]
Chen, J.; Lou, J.; Liu, T.; Wu, R.; Dong, X.; He, Q.; Yang, B.; Hu, Y. Synthesis and in-vitro antitumor activities of some mannich bases of 9-alkyl-1,2,3,4-tetrahydrocarbazole-1-ones. Arch. Pharm. (Weinheim), 2009, 342(3), 165-172.
[http://dx.doi.org/10.1002/ardp.200800179] [PMID: 19212985]
[75]
Barta, T.E.; Barabasz, A.F.; Foley, B.E.; Geng, L.; Hall, S.E.; Hanson, G.J.; Jenks, M.; Ma, W.; Rice, J.W.; Veal, J. Novel carbazole and acyl-indole antimitotics. Bioorg. Med. Chem. Lett., 2009, 19(11), 3078-3080.
[http://dx.doi.org/10.1016/j.bmcl.2009.04.010] [PMID: 19394222]
[76]
Kumar, T.S.; Mahadevan, K.M.; Kumara, M.N. Synthesis and cytotoxic studies of 2, 3- dimethylindoles and tetrahydrocarbazoles. Int. J. Pharm. Pharm. Sci., 2014, 6(2), 137-140.
[77]
Schönenberger, H.; Lippert, P. Cytostatics. 16. Antimicrobial and tumor-inhibiting properties of dithiourethane and studies on the mechanism of action. Pharmazie, 1972, 27(3), 139-145.
[PMID: 5049561]
[78]
Chaudhary, M.; Chaudhary, P. Anticancer activity of microwave assisted newly synthesized 2, 3, 4, 9-tetrahydro-1h-carbazole derivatives. Int. J. Pharm. Pharm. Sci., 2016, 8(4), 390-392.
[79]
Saravanabhavan, M.; Ebenazer, A.F.; Murugesan, V.; Sekar, M. Synthesis, spectroscopic characterization and biological evaluation of 1-(4′-hydroxybenzamido)-imine-1,2,3,4-tetrahydrocarbazole derivatives. J. Adv. Physics, 2017, 6(1), 30-40.
[http://dx.doi.org/10.1166/jap.2017.1286]
[80]
Kratz, F.; Beyer, U.; Roth, T.; Tarasova, N.; Collery, P.; Lechenault, F.; Cazabat, A.; Schumacher, P.; Unger, C.; Falken, U. Transferrin conjugates of doxorubicin: Synthesis, characterization, cellular uptake, and in vitro efficacy. J. Pharm. Sci., 1998, 87(3), 338-346.
[http://dx.doi.org/10.1021/js970246a] [PMID: 9523988]
[81]
Taj, T.; Kamble, R.R.; Gireesh, T.M.; Hunnur, R.K.; Margankop, S.B. One-pot synthesis of pyrazoline derivatised carbazoles as antitubercular, anticancer agents, their DNA cleavage and antioxidant activities. Eur. J. Med. Chem., 2011, 46(9), 4366-4373.
[http://dx.doi.org/10.1016/j.ejmech.2011.07.007] [PMID: 21802797]
[82]
Matiadis, D.; Sagnou, M. Pyrazoline hybrids as promising anticancer agents: An up-to-date overview. Int. J. Mol. Sci., 2020, 21(15), 5507.
[http://dx.doi.org/10.3390/ijms21155507] [PMID: 32752126]
[83]
Lanka, S; Lakinani, V; Kakani, S.R.R. Evaluation of anti-cancer activity of N-substituted tetrahydrocarbazoles. Inter. J. Pharm. Anal. Res., 2017, 6(2)
[84]
Roskoski, R., Jr ERK1/2 MAP kinases: Structure, function, and regulation. Pharmacol. Res., 2012, 66(2), 105-143.
[http://dx.doi.org/10.1016/j.phrs.2012.04.005] [PMID: 22569528]
[85]
Wilhelm, S.M.; Carter, C.; Tang, L.; Wilkie, D.; McNabola, A.; Rong, H.; Chen, C.; Zhang, X.; Vincent, P.; McHugh, M.; Cao, Y.; Shujath, J.; Gawlak, S.; Eveleigh, D.; Rowley, B.; Liu, L.; Adnane, L.; Lynch, M.; Auclair, D.; Taylor, I.; Gedrich, R.; Voznesensky, A.; Riedl, B.; Post, L.E.; Bollag, G.; Trail, P.A. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res., 2004, 64(19), 7099-7109.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-1443] [PMID: 15466206]
[86]
Catalanotti, F.; Solit, D.B.; Pulitzer, M.P.; Berger, M.F.; Scott, S.N.; Iyriboz, T.; Lacouture, M.E.; Panageas, K.S.; Wolchok, J.D.; Carvajal, R.D.; Schwartz, G.K.; Rosen, N.; Chapman, P.B. Phase II trial of MEK inhibitor selumetinib (AZD6244, ARRY-142886) in patients with BRAFV600E/K-mutated melanoma. Clin. Cancer Res., 2013, 19(8), 2257-2264.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-3476] [PMID: 23444215]
[87]
Knudsen, E.S.; Wang, J.Y.J. Targeting the RB-pathway in cancer therapy. Clin. Cancer Res., 2010, 16(4), 1094-1099.
[http://dx.doi.org/10.1158/1078-0432.CCR-09-0787] [PMID: 20145169]
[88]
Weinberg, R.A. The retinoblastoma protein and cell cycle control. Cell, 1995, 81(3), 323-330.
[89]
Nath, N.; Wang, S.; Betts, V.; Knudsen, E.; Chellappan, S. Apoptotic and mitogenic stimuli inactivate Rb by differential utilization of p38 and cyclin-dependent kinases. Oncogene, 2003, 22(38), 5986-5994.
[http://dx.doi.org/10.1038/sj.onc.1206843] [PMID: 12955077]
[90]
Popov, B.; Petrov, N. pRb-E2F signaling in life of mesenchymal stem cells: Cell cycle, cell fate, and cell differentiation. Genes Dis., 2014, 1(2), 174-187.
[http://dx.doi.org/10.1016/j.gendis.2014.09.007] [PMID: 30258863]
[91]
Kamada, H.; Tsutsumi, Y.; Yamamoto, Y.; Kihira, T.; Kaneda, Y.; Mu, Y.; Kodaira, H.; Tsunoda, S.I.; Nakagawa, S.; Mayumi, T. Antitumor activity of tumor necrosis factor-α conjugated with polyvinylpyrrolidone on solid tumors in mice. Cancer Res., 2000, 60(22), 6416-6420.
[PMID: 11103807]
[92]
Wu, T.; Dai, Y. Tumor microenvironment and therapeutic response. Cancer Lett., 2017, 387, 61-68.
[http://dx.doi.org/10.1016/j.canlet.2016.01.043] [PMID: 26845449]
[93]
Mantovani, A.; Marchesi, F.; Malesci, A.; Laghi, L.; Allavena, P. Tumour-associated macrophages as treatment targets in oncology. Nat. Rev. Clin. Oncol., 2017, 14(7), 399-416.
[http://dx.doi.org/10.1038/nrclinonc.2016.217] [PMID: 28117416]
[94]
Sica, A.; Mantovani, A. Macrophage plasticity and polarization: In vivo veritas. J. Clin. Invest., 2012, 122(3), 787-795.
[http://dx.doi.org/10.1172/JCI59643] [PMID: 22378047]
[95]
Saravanabhavan, M.; Badavath, V.N.; Maji, S.; Muhammad, S.; Sekar, M. Novel halogenated pyrido[2,3- a]carbazoles with enhanced aromaticity as potent anticancer and antioxidant agents: Rational design and microwave assisted synthesis. New J. Chem., 2019, 43(44), 17231-17240.
[http://dx.doi.org/10.1039/C8NJ06504G]
[96]
Saravanabhavan, M.; Murugesan, V.; Sekar, M. Microwave assisted synthesis of pyrido[2,3-a]carbazoles; investigation of in vitro DNA binding/cleavage, antioxidant and cytotoxicity studies. J. Photochem. Photobiol. B, 2014, 133, 145-152.
[http://dx.doi.org/10.1016/j.jphotobiol.2014.02.020] [PMID: 24727863]
[97]
Gribble, G.W. The alkaloids; Academic Press: New York, USA, 1990.
[98]
Harding, M.; Grummitt, A. 9-hydroxyellipticine and derivatives as chemotherapy agents. Mini Rev. Med. Chem., 2003, 3(2), 67-76.
[http://dx.doi.org/10.2174/1389557033405377] [PMID: 12570841]
[99]
Duncan, J.S.; Litchfield, D.W. Too much of a good thing: The role of protein kinase CK2 in tumorigenesis and prospects for therapeutic inhibition of CK2. Biochim. Biophys. Acta. Proteins Proteomics, 2008, 1784(1), 33-47.
[http://dx.doi.org/10.1016/j.bbapap.2007.08.017] [PMID: 17931986]
[100]
Rosales, M.; Pérez, G.V.; Ramón, A.C.; Cruz, Y.; Rodríguez-Ulloa, A.; Besada, V.; Ramos, Y.; Vázquez-Blomquist, D.; Caballero, E.; Aguilar, D.; González, L.J.; Zettl, K. Wiśniewski, J.R.; Yang, K.; Perera, Y.; Perea, S.E. Targeting of protein kinase CK2 in acute myeloid leukemia cells using the clinical-grade synthetic-peptide CIGB-300. Biomedicines, 2021, 9(7), 766.
[http://dx.doi.org/10.3390/biomedicines9070766] [PMID: 34356831]
[101]
Lau, A.; Villeneuve, N.; Sun, Z.; Wong, P.; Zhang, D. Dual roles of Nrf2 in cancer. Pharmacol. Res., 2008, 58(5-6), 262-270.
[http://dx.doi.org/10.1016/j.phrs.2008.09.003] [PMID: 18838122]
[102]
Geismann, C.; Arlt, A.; Sebens, S.; Schäfer, H. Cytoprotection “gone astray”: Nrf2 and its role in cancer. OncoTargets Ther., 2014, 7, 1497-1518.
[PMID: 25210464]
[103]
Basak, P.; Sadhukhan, P.; Sarkar, P.; Sil, P.C. Perspectives of the Nrf-2 signaling pathway in cancer progression and therapy. Toxicol. Rep., 2017, 4, 306-318.
[http://dx.doi.org/10.1016/j.toxrep.2017.06.002] [PMID: 28959654]
[104]
Patel, B.B.; Sengupta, R.; Qazi, S.; Vachhani, H.; Yu, Y.; Rishi, A.K.; Majumdar, A.P.N. Curcumin enhances the effects of 5-fluorouracil and oxaliplatin in mediating growth inhibition of colon cancer cells by modulating EGFR and IGF-1R. Int. J. Cancer, 2008, 122(2), 267-273.
[http://dx.doi.org/10.1002/ijc.23097] [PMID: 17918158]
[105]
Sathiya Kamatchi, T.; Mohamed Subarkhan, M.K.; Ramesh, R.; Wang, H. Małecki, J.G. Investigation into antiproliferative activity and apoptosis mechanism of new arene Ru(II) carbazole-based hydrazone complexes. Dalton Trans., 2020, 49(32), 11385-11395.
[http://dx.doi.org/10.1039/D0DT01476A] [PMID: 32776042]
[106]
Zeng, L.; Gupta, P.; Chen, Y.; Wang, E.; Ji, L.; Chao, H.; Chen, Z.S. The development of anticancer ruthenium (II) complexes: From single molecule compounds to nanomaterials. Chem. Soc. Rev., 2017, 46(19), 5771-5804.
[http://dx.doi.org/10.1039/C7CS00195A] [PMID: 28654103]
[107]
Thota, S.; Rodrigues, D.A.; Crans, D.C.; Barreiro, E.J. Ru (II) compounds: Next-generation anticancer metallotherapeutics? J. Med. Chem., 2018, 61(14), 5805-5821.
[http://dx.doi.org/10.1021/acs.jmedchem.7b01689] [PMID: 29446940]
[108]
Cagatay, E.; Akyildiz, V.; Ergun, Y.; Kayali, H.A. Synthesis of murrayaquinone‐a derivatives and investigation of potential anticancer properties. Chem. Biodivers., 2021, 18(11), e2100348.
[http://dx.doi.org/10.1002/cbdv.202100348] [PMID: 34459087]
[109]
Nishiyama, T.; Hatae, N.; Yoshimura, T.; Takaki, S.; Abe, T.; Ishikura, M.; Hibino, S.; Choshi, T. Concise synthesis of carbazole-1,4-quinones and evaluation of their antiproliferative activity against HCT-116 and HL-60 cells. Eur. J. Med. Chem., 2016, 121, 561-577.
[http://dx.doi.org/10.1016/j.ejmech.2016.05.065] [PMID: 27318980]
[110]
Xie, Q.; Su, M.; Liu, Y.; Zhang, D.; Li, Z.; Bai, M. Translocator protein (TSPO)-Targeted agents for photodynamic therapy of cancer. Photodiagn. Photodyn. Ther., 2021, 34, 102209.
[http://dx.doi.org/10.1016/j.pdpdt.2021.102209] [PMID: 33561573]
[111]
Baskaran, R.; Lee, J.; Yang, S.G. Clinical development of photodynamic agents and therapeutic applications. Biomater. Res., 2018, 22(1), 25.
[http://dx.doi.org/10.1186/s40824-018-0140-z] [PMID: 30275968]
[112]
Gavish, M.; Bachman, I.; Shoukrun, R.; Katz, Y.; Veenman, L.; Weisinger, G.; Weizman, A. Enigma of the peripheral benzodiazepine receptor. Pharmacol. Rev., 1999, 51(4), 629-650.
[PMID: 10581326]
[113]
Katz, Y; Ben-Baruch, G; Kloog, Y; Menczer, J; Gavish, M Increased density of peripheral benzodiazepine-binding sites in ovarian carcinomas as compared with benign ovarian tumours and normal ovaries. Clin. Sci. (London, England: 1979), 1990, 78(2), 155-158.
[http://dx.doi.org/10.1042/cs0780155]
[114]
Han, Z.; Slack, R.S.; Li, W.; Papadopoulos, V. Expression of peripheral benzodiazepine receptor (PBR) in human tumors: Relationship to breast, colorectal, and prostate tumor progression. J. Recept. Signal Transduct. Res., 2003, 23(2-3), 225-238.
[http://dx.doi.org/10.1081/RRS-120025210] [PMID: 14626449]
[115]
Vlodavsky, E.; Soustiel, J.F. Immunohistochemical expression of peripheral benzodiazepine receptors in human astrocytomas and its correlation with grade of malignancy, proliferation, apoptosis and survival. J. Neurooncol., 2006, 81(1), 1-7.
[http://dx.doi.org/10.1007/s11060-006-9199-9] [PMID: 16868661]
[116]
Ozkan, S.; Taskin-Tok, T.; Uzgoren-Baran, A.; Akbay, N. Multispectroscopic and computational investigation of CT-DNA binding properties with hydroxybenzylidene containing tetrahydrocarbazole derivative. J. Fluoresc., 2019, 29(1), 101-110.
[http://dx.doi.org/10.1007/s10895-018-2314-4] [PMID: 30361860]

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