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Mini-Reviews in Organic Chemistry

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ISSN (Print): 1570-193X
ISSN (Online): 1875-6298

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Mini-Review Article

Phenothiazine Derivatives as Potential Antiproliferative Agents: A Mini- Review

Author(s): Jude I. Ayogu* and Sunday T. Nwoba

Volume 19, Issue 3, 2022

Published on: 12 July, 2021

Page: [272 - 292] Pages: 21

DOI: 10.2174/1570193X18666210712112129

Price: $65

Abstract

Abstract: Research for discovering chemical entities with antiproliferative properties to combat globally rising cancer cases has witnessed tremendous interest in recent years. Phenothiazines possess novel antiproliferative potentials and have often be described as crucial sources of scaffolds for anticancer drug discovery. Some several phenothiazine-hybrid compounds recently synthesised are effective against various cancer cell lines with improved multidrug resistance. In synthesising these phenothiazine-derivatives, therapeutic potentials of the phenothiazines are exploited, and they are enriched by molecular hybridisation with moieties known to possess great pharmacological profiles. This article critically reviews the anticancer properties of phenothiazine derivatives and focuses on the possibility of the derivation of the leads for a further spectrum of antiproliferative activities.

Keywords: Phenothiazine, dithiocarbamate, anticancer, apoptosis, glioblastoma, chalcones.

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[1]
Sivaramakarthikeyan, R.; Iniyaval, S.; Padmavathy, K.; Liew, H-S.; Looi, C-K.; Mai, C-W.; Ramalingan, C. Phenothiazine and amide-ornamented dihydropyridines via a molecular hybridization approach: Design, synthesis, biological evaluation and molecular docking studies. New J. Chem., 2019, 43, 17046-17057.
[http://dx.doi.org/10.1039/C9NJ03394G]
[2]
(a) Ayogu, J.I.; Odoh, A.S. Prospects and therapeutic applications of cardiac glycosides in cancer remediation. ACS Comb. Sci., 2020, 22(11), 543-553.
(b) Zhang, J.; Ming, C.; Zhang, W.; Okechukwu, P.N.; Morak-Młodawska, B.; Pluta, K.; Jeleń, M.; Akim, A.M.; Ang, K-P.; Ooi, K.K. 10H-3,6-Diazaphenothiazine induces G2/M phase cell cycle arrest and caspase-dependent apoptosis and inhibits cell invasion of A2780 ovarian carcinoma cells through the regulation of NF-κB and (BIRC6-XIAP) complexes. Drug Des. Devel. Ther., 2017, 11, 3045-3063.
[http://dx.doi.org/10.2147/DDDT.S144415] [PMID: 29123378]
[3]
(a) Torre, L.A.; Siegel, R.L.; Ward, E.M.; Jemal, A. Global cancer incidence and mortality rates and trends--An update. Cancer Epidemiol. Biomarkers Prev., 2016, 25(1), 16-27.
[http://dx.doi.org/10.1158/1055-9965.EPI-15-0578] [PMID: 26667886]
(b) Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2015. CA Cancer J. Clin., 2015, 65(1), 5-29.
[http://dx.doi.org/10.3322/caac.21254] [PMID: 25559415]
(c) Nuyttens, J.J.; Rust, P.F.; Thomas, C.R., Jr; Turrisi, A.T. Surgery versus radiation therapy for patients with aggressive fibromatosis or desmoid tumors: A comparative review of 22 articles. Cancer, 2000, 88(7), 1517-1523.
[http://dx.doi.org/10.1002/(SICI)1097-0142(20000401)88:7<1517:AID-CNCR3>3.0.CO;2-9] [PMID: 10738207]
[4]
Morak-Młodawska, B.; Pluta, K.; Latocha, M.; Jeleń, M.; Kuśmierz, D.; Suwińska, K.; Shkurenko, A.; Czuba, Z.; Jurzak, M. 10H-1,9-diazaphenothiazine and its 10-derivatives: Synthesis, characterisation and biological evaluation as potential anticancer agents. J. Enzyme Inhib. Med. Chem., 2019, 34(1), 1298-1306.
[http://dx.doi.org/10.1080/14756366.2019.1639695] [PMID: 31307242]
[5]
(a) Gregorić, T.; Sedić, M.; Grbčić, P.; Tomljenović Paravić, A.; Kraljević Pavelić, S.; Cetina, M.; Vianello, R.; Raić-Malić, S. Novel pyrimidine-2,4-dione-1,2,3-triazole and furo[2,3-d]pyrimi-dine-2-one-1,2,3-triazole hybrids as potential anti-cancer agents: Synthesis, computational and X-ray analysis and biological evaluation. Eur. J. Med. Chem., 2017, 125, 1247-1267.
[http://dx.doi.org/10.1016/j.ejmech.2016.11.028] [PMID: 27875779]
(b) Eckhardt, S. Recent progress in the development of anticancer agents. Curr. Med. Chem. Anticancer Agents, 2002, 2(3), 419-439.
[http://dx.doi.org/10.2174/1568011024606389] [PMID: 12678741]
[6]
(a) Bajaj, S.; Asati, V.; Singh, J.; Roy, P.P. 1,3,4-Oxadiazoles: An emerging scaffold to target growth factors, enzymes and kinases as anticancer agents. Eur. J. Med. Chem., 2015, 97, 124-141.
[http://dx.doi.org/10.1016/j.ejmech.2015.04.051] [PMID: 25965776]
(b) Yugandhar, D.; Nayak, V.L.; Archana, S.; Shekar, K.C.; Srivastava, A.K. Design, synthesis and anticancer properties of novel oxa/azaspiro[4,5]trienones as potent apoptosis inducers through mitochondrial disruption. Eur. J. Med. Chem., 2015, 101, 348-357.
[http://dx.doi.org/10.1016/j.ejmech.2015.06.050] [PMID: 26163220]
[7]
(a) Wu, C-H.; Bai, L-Y.; Tsai, M-H.; Chu, P-C.; Chiu, C-F.; Chen, M.Y.; Chiu, S-J.; Chiang, J-H.; Weng, J-R. Ultrastructural characterization of the lower motor system in a mouse model of krabbe disease. Sci. Rep., 2016, 6, 1-11.
[http://dx.doi.org/10.1038/s41598-016-0001-8] [PMID: 28442746]
(b) Jeleń, M.; Pluta, K.; Zimecki, M.; Morak-Młodawska, B.; Artym, J.; Kocięba, M. 6-Substituted 9-fluoroquino[3,2-b]benzo[1,4]thiazines display strong antiproliferative and antitumor properties. Eur. J. Med. Chem., 2015, 89, 411-420.
[http://dx.doi.org/10.1016/j.ejmech.2014.10.070] [PMID: 25462256]
(c) Lee, M.S.; Johansen, L.; Zhang, Y.; Wilson, A.; Keegan, M.; Avery, W.; Elliott, P.; Borisy, A.A.; Keith, C.T. The novel combination of chlorpromazine and pentamidine exerts synergistic antiproliferative effects through dual mitotic action. Cancer Res., 2007, 67(23), 11359-11367.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-2235] [PMID: 18056463]
(d) Varga, B.; Csonka, Á.; Csonka, A.; Molnár, J.; Amaral, L.; Spengler, G. Possible biological and clinical applications of phenothiazines. Anticancer Res., 2017, 37(11), 5983-5993.
[PMID: 29061777]
[8]
(a) Motohashi, N.; Kawase, M.; Saito, S.; Sakagami, H. Antitumor potential and possible targets of phenothiazine-related compounds. Curr. Drug Targets, 2000, 1(3), 237-245.
[http://dx.doi.org/10.2174/1389450003349191] [PMID: 11465073]
(b) Sadanandam, Y.S.; Shetty, M.M.; Rao, A.B.; Rambabu, Y. 10H-Phenothiazines: A new class of enzyme inhibitors for inflam-matory diseases. Eur. J. Med. Chem., 2009, 44(1), 197-202.
[http://dx.doi.org/10.1016/j.ejmech.2008.02.028] [PMID: 18400337]
(c) Pluta, K.; Morak-Młodawska, B.; Jeleń, M. Recent progress in biological activities of synthesized phenothiazines. Eur. J. Med. Chem., 2011, 46(8), 3179-3189.
[http://dx.doi.org/10.1016/j.ejmech.2011.05.013] [PMID: 21620536]
(d) Sarmiento, G.P.; Vitale, R.G.; Afeltra, J.; Moltrasio, G.Y.; Moglioni, A.G. Synthesis and antifungal activity of some substituted phenothiazines and related compounds. Eur. J. Med. Chem., 2011, 46(1), 101-105.
[http://dx.doi.org/10.1016/j.ejmech.2010.10.019] [PMID: 21093111]
(e) Bansode, T.N.; Shelke, J.V.; Dongre, V.G. Synthesis and antimicrobial activity of some new N-acyl substituted phenothiazines. Eur. J. Med. Chem., 2009, 44(12), 5094-5098.
[http://dx.doi.org/10.1016/j.ejmech.2009.07.006] [PMID: 19651462]
[9]
(a) Baral, P.K.; Swayampakula, M.; Rout, M.K.; Kav, N.N.; Spyracopoulos, L.; Aguzzi, A.; James, M.N. Structural basis of prion inhibition by phenothiazine compounds. Structure, 2014, 22(2), 291-303.
[http://dx.doi.org/10.1016/j.str.2013.11.009] [PMID: 24373770]
(b) Korth, C.; May, B.C.; Cohen, F.E.; Prusiner, S.B. Acridine and phenothiazine derivatives as pharmacotherapeutics for prion disease. Proc. Natl. Acad. Sci. USA, 2001, 98(17), 9836-9841.
[http://dx.doi.org/10.1073/pnas.161274798] [PMID: 11504948]
[10]
Pluta, K.; Jeleń, M.; Morak-Młodawska, B.; Zimecki, M.; Artym, J.; Kocięba, M.; Zaczyńska, E. Azaphenothiazines - promising phenothiazine derivatives. An insight into nomenclature, synthesis, structure elucidation and biological properties. Eur. J. Med. Chem., 2017, 138, 774-806.
[http://dx.doi.org/10.1016/j.ejmech.2017.07.009] [PMID: 28734245]
[11]
Bennett, J.L.; Kooi, K.A. Five phenothiazine derivatives evaluation and toxicity studies. Arch. Gen. Psychiatry, 1961, 4, 413-418.
[http://dx.doi.org/10.1001/archpsyc.1961.01710100093011]
[12]
Dastidar, S.G.; Kristiansen, J.E.; Molnar, J.; Amaral, L. Role of phenothiazines and structurally similar compounds of plant origin in the fight against infections by drug resistant bacteria. Antibiotics (Basel), 2013, 2(1), 58-72.
[http://dx.doi.org/10.3390/antibiotics2010058] [PMID: 27029292]
[13]
Mosnaim, A.D.; Ranade, V.V.; Wolf, M.E.; Puente, J.; Antonieta Valenzuela, M. Phenothiazine molecule provides the basic chemical structure for various classes of pharmacotherapeutic agents. Am. J. Ther., 2006, 13(3), 261-273.
[http://dx.doi.org/10.1097/01.mjt.0000212897.20458.63] [PMID: 16772768]
[14]
Yue, H.; Huang, D.; Qin, L.; Zheng, Z.; Hua, L.; Wang, G.; Huang, J.; Huang, H. Targeting lung cancer stem cells with antipsychological drug thioridazine. BioMed Res. Int., 2016, 2016Article ID 6709828
[15]
Ghinet, A.; Moise, I-M.; Rigo, B.; Homerin, G.; Farce, A.; Dubois, J.; Bîcu, E. Studies on phenothiazines: New microtubule-interacting compounds with phenothiazine A-ring as potent antineoplastic agents. Bioorg. Med. Chem., 2016, 24(10), 2307-2317.
[http://dx.doi.org/10.1016/j.bmc.2016.04.001] [PMID: 27073050]
[16]
Abuhaie, C-M.; Bîcu, E.; Rigo, B.; Gautret, P.; Belei, D.; Farce, A.; Dubois, J.; Ghinet, A. Synthesis and anticancer activity of analogues of phenstatin, with a phenothiazine A-ring, as a new class of microtubule-targeting agents. Bioorg. Med. Chem. Lett., 2013, 23(1), 147-152.
[http://dx.doi.org/10.1016/j.bmcl.2012.10.135] [PMID: 23200248]
[17]
Ayogu, J.I.; Ezema, B.E.; Ezema, C.G. Synthesis and antimicrobial screening of novel benzoxazinophenothiazine derivatives. Asian J. Chem., 2015, 27, 4115-4119.
[18]
(a) Fu, D-J.; Fu, L.; Liu, Y-C.; Wang, J-W.; Wang, Y-Q.; Han, B-K.; Li, X-R.; Zhang, C.; Li, F.; Song, J. Ror2 signaling regulates Golgi structure and transport through IFT20 for tumor invasiveness. Sci. Rep., 2017, 7, 1-12.
[http://dx.doi.org/10.1038/s41598-016-0028-x] [PMID: 28127051]
(b) Dheer, D.; Singh, V.; Shankar, R. Medicinal attributes of 1,2,3-triazoles: Current developments. Bioorg. Chem., 2017, 71, 30-54.
[http://dx.doi.org/10.1016/j.bioorg.2017.01.010] [PMID: 28126288]
(c) Bozorov, K.; Zhao, J.; Aisa, H.A. 1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview. Bioorg. Med. Chem., 2019, 27(16), 3511-3531.
[http://dx.doi.org/10.1016/j.bmc.2019.07.005] [PMID: 31300317]
(d) Pingaew, R.; Mandi, P.; Nantasenamat, C.; Prachayasittikul, S.; Ruchirawat, S.; Prachayasittikul, V. Design, synthesis and molecular docking studies of novel N-benzenesulfonyl-1,2,3,4-tetrahydroisoquinoline-based triazoles with potential anticancer activity. Eur. J. Med. Chem., 2014, 81, 192-203.
[http://dx.doi.org/10.1016/j.ejmech.2014.05.019] [PMID: 24836071]
(e) Holla, B.S.; Poojary, K.N.; Rao, B.S.; Shivananda, M.K. New bis-aminomercaptotriazoles and bis-triazolothiadiazoles as possible anticancer agents. Eur. J. Med. Chem., 2002, 37(6), 511-517.
[http://dx.doi.org/10.1016/S0223-5234(02)01358-2] [PMID: 12204477]
(f) Holla, B.S.; Veerendra, B.; Shivananda, M.; Poojary, B. Synthesis characterization and anticancer activity studies on some Mannich bases derived from 1,2,4-triazoles. Eur. J. Med. Chem., 2003, 38, 759-767.
[http://dx.doi.org/10.1016/S0223-5234(03)00128-4] [PMID: 12932907]
[19]
(a) Vatmurge, N.S.; Hazra, B.G.; Pore, V.S.; Shirazi, F.; Chavan, P.S.; Deshpande, M.V. Synthesis and antimicrobial activity of beta-lactam-bile acid conjugates linked via triazole. Bioorg. Med. Chem. Lett., 2008, 18(6), 2043-2047.
[http://dx.doi.org/10.1016/j.bmcl.2008.01.102] [PMID: 18267360]
(b) Vatmurge, N.S.; Hazra, B.G.; Pore, V.S.; Shirazi, F.; Deshpande, M.V.; Kadreppa, S.; Chattopadhyay, S.; Gonnade, R.G. Synthesis and biological evaluation of bile acid dimers linked with 1,2,3-triazole and bis-beta-lactam. Org. Biomol. Chem., 2008, 6(20), 3823-30.
[20]
Zhang, J-X.; Guo, J-M.; Zhang, T-T.; Lin, H-J.; Qi, N-S.; Li, Z-G.; Zhou, J-C.; Zhang, Z-Z. Antiproliferative phenothiazine hybrids as novel apoptosis inducers against MCF-7 breast cancer. Molecules, 2018, 23, 1288.
[http://dx.doi.org/10.3390/molecules23061288]
[21]
Ma, X-H.; Liu, N.; Lu, J-L.; Zhao, J.; Zhang, X-J. Design, synthesis and antiproliferative activity of novel phenothiazine-1,2,3-triazole analogues. J. Chem. Res., 2017, 41, 696-698.
[http://dx.doi.org/10.3184/174751917X15122516000140]
[22]
Viegas-Junior, C.; Danuello, A.; da Silva Bolzani, V.; Barreiro, E.J.; Fraga, C.A.M. Molecular hybridization: A useful tool in the design of new drug prototypes. Curr. Med. Chem., 2007, 14(17), 1829-1852.
[http://dx.doi.org/10.2174/092986707781058805] [PMID: 17627520]
[23]
(a) Agalave, S.G.; Maujan, S.R.; Pore, V.S. Click chemistry: 1,2,3-triazoles as pharmacophores. Chem. Asian J., 2011, 6(10), 2696-2718.
[http://dx.doi.org/10.1002/asia.201100432] [PMID: 21954075]
(b) Kolb, H.C.; Sharpless, K.B. The growing impact of click chemistry on drug discovery. Drug Discov. Today, 2003, 8(24), 1128-1137.
[http://dx.doi.org/10.1016/S1359-6446(03)02933-7] [PMID: 14678739]
[24]
Morak-Młodawska, B.; Pluta, K.; Latocha, M.; Jeleń, M.; Kuśmierz, D. Design, synthesis, and structural characterization of novel diazaphenothiazines with 1,2,3-triazole substituents as promising antiproliferative agents. Molecules, 2019, 24, 4388.
[http://dx.doi.org/10.3390/molecules24234388]
[25]
Ståhlberg, A.; Bengtsson, M. Single-cell gene expression profiling using reverse transcription quantitative real-time PCR. Methods, 2010, 50(4), 282-288.
[http://dx.doi.org/10.1016/j.ymeth.2010.01.002] [PMID: 20064613]
[26]
Liu, N.; Jin, Z.; Zhang, J.; Jin, J. Antitumor evaluation of novel phenothiazine derivatives that inhibit migration and tubulin polymerization against gastric cancer MGC-803 cells. Invest. New Drugs, 2019, 37(1), 188-198.
[http://dx.doi.org/10.1007/s10637-018-0682-x] [PMID: 30345465]
[27]
(a) Len, C.; Boulogne-Merlot, A-S.; Postel, D.; Ronco, G.; Villa, P.; Goubert, C.; Jeufrault, E.; Mathon, B.; Simon, H. Synthesis and antifungal activity of novel bis(dithiocarbamate) derivatives of glycerol. J. Agric. Food Chem., 1996, 44, 2856-2858.
[http://dx.doi.org/10.1021/jf950751y]
(b) Manav, N.; Mishra, A.K.; Kaushik, N.K. In vitro antitumour and antibacterial studies of some Pt(IV) dithiocarbamate complexes. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2006, 65(1), 32-35.
[http://dx.doi.org/10.1016/j.saa.2005.09.023] [PMID: 16522376]
(c) Vullo, D.; Durante, M.; Di Leva, F.S.; Cosconati, S.; Masini, E.; Scozzafava, A.; Novellino, E.; Supuran, C.T.; Carta, F. Monothio-carbamates strongly inhibit carbonic anhydrases in vitro and possess intraocular pressure lowering activity in an animal model of glaucoma. J. Med. Chem., 2016, 59(12), 5857-5867.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00462] [PMID: 27253845]
(d) Li, R-D.; Wang, H-L.; Li, Y-B.; Wang, Z-Q.; Wang, X.; Wang, Y-T.; Ge, Z-M.; Li, R-T. Discovery and optimization of novel dual dithiocarbamates as potent anticancer agents. Eur. J. Med. Chem., 2015, 93, 381-391.
[http://dx.doi.org/10.1016/j.ejmech.2015.02.030] [PMID: 25725374]
(e) Altıntop, M.D.; Sever, B.; Akalın Çiftçi, G.; Kucukoglu, K.; Özdemir, A.; Soleimani, S.S.; Nadaroglu, H.; Kaplancıklı, Z.A. Synthesis and evaluation of new benzodioxole-based dithiocarba-mate derivatives as potential anticancer agents and hCA-I and hCA-II inhibitors. Eur. J. Med. Chem., 2017, 125, 190-196.
[http://dx.doi.org/10.1016/j.ejmech.2016.09.035] [PMID: 27657811]
(f) Bozdag, M.; Carta, F.; Vullo, D.; Akdemir, A.; Isik, S.; Lanzi, C.; Scozzafava, A.; Masini, E.; Supuran, C.T. Synthesis of a new series of dithiocarbamates with effective human carbonic anhydrase inhibitory activity and antiglaucoma action. Bioorg. Med. Chem., 2015, 23(10), 2368-2376.
[http://dx.doi.org/10.1016/j.bmc.2015.03.068] [PMID: 25846066]
[28]
Fu, D-J.; Zhao, R-H.; Li, J-H.; Yang, J-J.; Mao, R-W.; Wu, B-W.; Li, P.; Zi, X-L.; Zhang, Q-Q.; Cai, H-J.; Zhang, S.Y.; Zhang, Y.B.; Liu, H.M. Molecular diversity of phenothiazines: Design and synthesis of phenothiazine-dithiocarbamate hybrids as potential cell cycle blockers. Mol. Divers., 2017, 21(4), 933-942.
[http://dx.doi.org/10.1007/s11030-017-9773-4] [PMID: 28785928]
[29]
Duan, Y-C.; Ma, Y-C.; Zhang, E.; Shi, X-J.; Wang, M-M.; Ye, X-W.; Liu, H-M. Design and synthesis of novel 1,2,3-triazole-dithiocarbamate hybrids as potential anticancer agents. Eur. J. Med. Chem., 2013, 62, 11-19.
[http://dx.doi.org/10.1016/j.ejmech.2012.12.046] [PMID: 23353743]
[30]
Fernández-Calienes, A.; Pellón, R.; Docampo, M.; Fascio, M.; D’Accorso, N.; Maes, L.; Mendiola, J.; Monzote, L.; Gille, L.; Rojas, L. Antimalarial activity of new acridinone derivatives. Biomed. Pharmacother., 2011, 65(3), 210-214.
[http://dx.doi.org/10.1016/j.biopha.2011.04.001] [PMID: 21641752]
[31]
Belmont, P.; Dorange, I. Acridine/acridone: A simple scaffold with a wide range of application in oncology. Expert Opin. Ther. Pat., 2008, 18, 1211-1224.
[http://dx.doi.org/10.1517/13543776.18.11.1211]
[32]
(a) Verones, V.; Flouquet, N.; Lecoeur, M.; Lemoine, A.; Farce, A.; Baldeyrou, B.; Mahieu, C.; Wattez, N.; Lansiaux, A.; Goossens, J-F.; Berthelot, P.; Lebegue, N. Synthesis, antipro-liferative activity and tubulin targeting effect of acridinone and dioxophenothiazine derivatives. Eur. J. Med. Chem., 2013, 59, 39-47.
[http://dx.doi.org/10.1016/j.ejmech.2012.10.051] [PMID: 23202849]
(b) Moriya, K.; Rivera, J.; Odom, S.; Sakuma, Y.; Muramato, K.; Yoshiuchi, T.; Miyamoto, M.; Yamada, K. ER-27319, an acridone-related compound, inhibits release of antigen-induced allergic mediators from mast cells by selective inhibition of fcepsilon receptor I-mediated activation of Syk. Proc. Natl. Acad. Sci. USA, 1997, 94(23), 12539-12544.
[http://dx.doi.org/10.1073/pnas.94.23.12539] [PMID: 9356485]
[33]
Kumar, P.; Gupta, R. The wonderful world of pyridine-2,6-dicarboxamide based scaffolds. Dalton Trans., 2016, 45(47), 18769-18783.
[http://dx.doi.org/10.1039/C6DT03578G] [PMID: 27819372]
[34]
Prinz, H.; Chamasmani, B.; Vogel, K.; Böhm, K.J.; Aicher, B.; Gerlach, M.; Günther, E.G.; Amon, P.; Ivanov, I.; Müller, K. N-benzoylated phenoxazines and phenothiazines: Synthesis, antiproliferative activity, and inhibition of tubulin polymerization. J. Med. Chem., 2011, 54(12), 4247-4263.
[http://dx.doi.org/10.1021/jm200436t] [PMID: 21563750]
[35]
Ghorab, M.M.; Alsaid, M.S.; Samir, N.; Abdel-Latif, G.A.; Soliman, A.M.; Ragab, F.A.; Abou El Ella, D.A. Aromatase inhibitors and apoptotic inducers: Design, synthesis, anticancer activity and molecular modeling studies of novel phenothiazine derivatives carrying sulfonamide moiety as hybrid molecules. Eur. J. Med. Chem., 2017, 134, 304-315.
[http://dx.doi.org/10.1016/j.ejmech.2017.04.028] [PMID: 28427017]
[36]
Skehan, P.; Storeng, R.; Scudiero, D.; Monks, A.; McMahon, J.; Vistica, D.; Warren, J.T.; Bokesch, H.; Kenney, S.; Boyd, M.R. New colorimetric cytotoxicity assay for anticancer-drug screening. J. Natl. Cancer Inst., 1990, 82(13), 1107-1112.
[http://dx.doi.org/10.1093/jnci/82.13.1107] [PMID: 2359136]
[37]
Creagh, E.M.; Conroy, H.; Martin, S.J. Caspase-activation pathways in apoptosis and immunity. Immunol. Rev., 2003, 193, 10-21.
[http://dx.doi.org/10.1034/j.1600-065X.2003.00048.x] [PMID: 12752666]
[38]
(a) Young, C.J.; Richard, K.; Beruar, A.; Lo, S.Y.; Siemann, S. An investigation of the pH dependence of copper-substituted anthrax lethal factor and its mechanistic implications. J. Inorg. Biochem., 2018, 182, 1-8.
[http://dx.doi.org/10.1016/j.jinorgbio.2018.01.015] [PMID: 29407865]
[39]
(b) Dos Santos, T.A.R.; da Silva, A.C.; Silva, E.B.; Gomes, P.A.; Espíndola, J.W.P.; Cardoso, M.V.; Moreira, D.R.M.; Leite, A.C.L.; Pereira, V.R. Antitumor and immunomodulatory activities of thiosemicarbazones and 1,3-thiazoles in Jurkat and HT-29 cells. Biomed. Pharmacother., 2016, 82, 555-560.
[http://dx.doi.org/10.1016/j.biopha.2016.05.038] [PMID: 27470396]
[40]
Alsharekh, M.M.; Althagafi, I.I.; Shaaban, M.R.; Farghaly, T.A. Microwave-assisted and thermal synthesis of nanosized thiazolyl-phenothiazine derivatives and their biological activities. Res. Chem. Intermed., 2019, 45, 127-154.
[http://dx.doi.org/10.1007/s11164-018-3594-7]
[41]
Krishnan, K.G.; Kumar, C.U.; Lim, W-M.; Mai, C-W.; Thanikachalam, P.V.; Ramalingan, C. Novel cyanoacetamide integrated phenothiazines: Synthesis, characterization, computational studies and in vitro antioxidant and anticancer evaluations. J. Mol. Struct., 2020, 1199127037
[http://dx.doi.org/10.1016/j.molstruc.2019.127037]
[42]
Motohashi, N. Phenothiazines and calmodulin. Anticancer Res., 1991, 11(3), 1125-64.
[43]
(a) Sakagami, H.; Takahashi, H.; Yoshida, H.; Yamamura, M.; Fukuchi, K.; Gomi, K.; Motohashi, N.; Takeda, M. Induction of DNA fragmentation in human myelogenous leukaemic cell lines by phenothiazine-related compounds. Anticancer Res., 1995, 15(6B), 2533-2540.
[PMID: 8669819]
(b) Motohashi, N.; Sakagami, H.; Kamata, K.; Yamamoto, Y. Cytotoxicity and differentiation-inducing activity of phenothiazine and benzo[a]phenothiazine derivatives. Anticancer Res., 1991, 11(5), 1933-1937.
[PMID: 1662929]
[44]
Motohashi, N.; Kurihara, T.; Sakagami, H.; Szabo, D.; Csuri, K.; Molnár, J. Chemical structure and tumor type specificity of “half-mustard type” phenothiazines. Anticancer Res., 1999, 19(3A), 1859-1864.
[PMID: 10470128]
[45]
Wuonola, M.A.; Palfreyman, M.G.; Motohashi, N.; Kawase, M.; Gabay, S.; Gupta, R.R.; Molnár, J. The primary in vitro anticancer activity of “half-mustard type” phenothiazines in NCI’s revised anticancer screening paradigm. Anticancer Res., 1998, 18(1A), 337-348.
[PMID: 9568100]
[46]
(a) Nagy, S.; Argyelan, G.; Molnár, J.; Kawase, M.; Motohashi, N. Antitumor activity of phenothiazine-related compounds. Anticancer Res., 1996, 16(4A), 1915-1918.
[PMID: 8712720]
(b) Motohashi, N.; Kawase, M.; Kurihara, T.; Hevér, A.; Nagy, S.; Ocsocvszki, I.; Tanaka, M.; Molnár, J. Synthesis and antitumor activity of 1-[2-(chloroethyl)-3-(2-substituted-10H-phenothiazin-10-yl)alkyl- 1-urea s as potent anticancer agents. Anticancer Res., 1996, 16(5A), 2525-2532.
[PMID: 8917346]
[47]
Motohashi, N.; Kawase, M.; Saito, S.; Kurihara, T.; Satoh, K.; Nakashima, H.; Premanathan, M.; Arakaki, R.; Sakagami, H.; Molnár, J. Synthesis and biological activity of N-acylpheno-thiazines. Int. J. Antimicrob. Agents, 2000, 14(3), 203-207.
[http://dx.doi.org/10.1016/S0924-8579(99)00156-9] [PMID: 10773488]
[48]
(a) Motohashi, N.; Kawase, M.; Satoh, K.; Sakagami, H. Cytotoxic potential of phenothiazines. Curr. Drug Targets, 2006, 7(9), 1055-1066.
[http://dx.doi.org/10.2174/138945006778226624] [PMID: 17017885]
(b) Aaron, J.; Seye, M.G.; Trajkovska, S.; Motohashi, N. .Bioactive Phenothiazines and Benzo[a]phenothiazines: Spectroscopic Studies, and Biological and Biomedical Properties and Applications. In: Bioactive Heterocycles VII; Springer: Berlin, 2008, pp. 153-231;
[http://dx.doi.org/10.1007/7081_2008_125]
[49]
Okumura, H.; Nakazawa, J.; Tsuganezawa, K.; Usui, T.; Osada, H.; Matsumoto, T.; Tanaka, A.; Yokoyama, S. Phenothiazine and carbazole-related compounds inhibit mitotic kinesin Eg5 and trigger apoptosis in transformed culture cells. Toxicol. Lett., 2006, 166(1), 44-52.
[http://dx.doi.org/10.1016/j.toxlet.2006.05.011] [PMID: 16814965]
[50]
Pluta, K.; Jeleń, M.; Morak-Młodawska, B.; Zimecki, M.; Artym, J.; Kocięba, M. Anticancer activity of newly synthesized azaphenothiazines from NCI’s anticancer screening bank. Pharmacol. Rep., 2010, 62(2), 319-332.
[http://dx.doi.org/10.1016/S1734-1140(10)70272-3] [PMID: 20508288]
[51]
Morak-Mlodawska, B.; Pluta, K. Synthesis of novel dipyrido-1,4-thiazines. Heterocycles, 2007, 71, 1347-1361.
[http://dx.doi.org/10.3987/COM-07-11035]
[52]
(a) Jelen, M.; Pluta, K. Synthesis of 6-aminoalkyldiquino-1,4-thiazines and their acyl and sulfonyl derivative. Heterocycles, 2008, 75, 859-870; (b) Morak-Mlodawska, B.; Pluta, K. Acyl and sulfonyl derivatives of 10-aminoalkyl-2,7-diazaphenothiazines. Heterocycles, 2009, 78, 1289-1298.
[53]
Pluta, K.; Maślankiewicz, A.; Szmielew, M.N. N-dialkylamino-alkyl substituted quinobenzo[1,4]thiazines and diquino[1,4]thia-zines. Phosphorus Sulfur Silicon Relat. Elem., 2000, 159, 79-86.
[http://dx.doi.org/10.1080/10426500008043652]
[54]
Jeleń, M.; Pluta, K.; Latocha, M.; Morak-Młodawska, B.; Suwińska, K.; Kuśmierz, D. Evaluation of angularly condensed diquinothiazines as potential anticancer agents. Bioorg. Chem., 2019, 87, 810-820.
[http://dx.doi.org/10.1016/j.bioorg.2019.04.005] [PMID: 30981160]
[55]
Zimecki, M.; Artym, J.; Kocięba, M.; Pluta, K.; Morak-Młodawska, B.; Jeleń, M. The immunosuppressive activities of newly synthesized azaphenothiazines in human and mouse models. Cell. Mol. Biol. Lett., 2009, 14(4), 622-635.
[http://dx.doi.org/10.2478/s11658-009-0025-1] [PMID: 19557312]
[56]
Morak-Młodawska, B.; Pluta, K.; Latocha, M.; Jeleń, M. Synthesis, spectroscopic characterization, and anticancer activity of new 10-substituted 1,6-diazaphenothiazines. Med. Chem. Res., 2016, 25(11), 2425-2433.
[http://dx.doi.org/10.1007/s00044-016-1646-3] [PMID: 27818603]
[57]
Morak-Młodawska, B.; Pluta, K.; Zimecki, M.; Jeleń, M.; Artym, J.; Kocięba, M. Synthesis and selected immunological properties of 10-substituted 1,8-diazaphenothiazines. Med. Chem. Res., 2015, 24(4), 1408-1418.
[http://dx.doi.org/10.1007/s00044-014-1220-9] [PMID: 25750499]
[58]
Tandon, V.K.; Maurya, H.K.; Tripathi, A. ShivaKeshava, G.; Shukla, P.K.; Srivastava, P.; Panda, D. 2,3-disubstituted-1,4-naphthoquinones, 12H-benzo(b)phenothiazine-6,11-diones and related compounds: Synthesis and biological evaluation as potential antiproliferative and antifungal agents. Eur. J. Med. Chem., 2009, 44, 1086-1092.
[http://dx.doi.org/10.1016/j.ejmech.2008.06.025] [PMID: 18708272]
[59]
Morak-Młodawska, B.; Pluta, K.; Latocha, M.; Suwińska, K.; Jeleń, M.; Kuśmierz, D. 3,6-Diazaphenothiazines as potential lead molecules - synthesis, characterization and anticancer activity. J. Enzyme Inhib. Med. Chem., 2016, 31(6), 1512-1519.
[http://dx.doi.org/10.3109/14756366.2016.1151014] [PMID: 26950280]
[60]
Omoruyi, S.; Ekpo, O.; Semenya, D.; Jardine, A.; Prince, S. Exploitation of a novel phenothiazine derivative for its anti-cancer activities in malignant glioblastoma. Apoptosis, 2020, 1-14.
[61]
Lin, Y-J.; Chiu, H-Y.; Chiou, M-J.; Huang, Y-C.; Wei, K-C.; Kuo, C-F.; Hsu, J-T.; Chen, P-Y. Trends in the incidence of primary malignant brain tumors in Taiwan and correlation with comorbidities: A population-based study. Clin. Neurol. Neurosurg., 2017, 159, 72-82.
[http://dx.doi.org/10.1016/j.clineuro.2017.05.021] [PMID: 28687250]
[62]
Luan, Y.; Liu, J.; Gao, J.; Wang, J. The design and synthesis of novel phenothiazine derivatives as potential cytotoxic agents. Lett. Drug Des. Discov., 2020, 17, 57-67.
[http://dx.doi.org/10.2174/1570180816666181115112236]
[63]
Szliszka, E.; Mazur, B.; Zydowicz, G.; Czuba, Z.P.; Król, W. TRAIL-induced apoptosis and expression of death receptor TRAIL-R1 and TRAIL-R2 in bladder cancer cells. Folia Histochem. Cytobiol., 2009, 47(4), 579-585.
[PMID: 20430723]
[64]
(a) Parveen, P.; Usha, P.; Naik, V.V.; Sultana, S.S.; Ramya, M.G. Synthesis of chalcones and evaluation of their anti-microbial activity. Res. J. Pharm. Dos. Forms Technol., 2014, 6, 26-32.
(b) Szliszka, E.; Czuba, Z.P.; Mazur, B.; Sedek, L.; Paradysz, A.; Krol, W. Chalcones enhance TRAIL-induced apoptosis in prostate cancer cells. Int. J. Mol. Sci., 2009, 11(1), 1-13.
[http://dx.doi.org/10.3390/ijms11010001] [PMID: 20161998]
(c) Nowakowska, Z. A review of anti-infective and anti-inflam-matory chalcones. Eur. J. Med. Chem., 2007, 42(2), 125-137.
[http://dx.doi.org/10.1016/j.ejmech.2006.09.019] [PMID: 17112640]
(d) Echeverria, C.; Santibañez, J.F.; Donoso-Tauda, O.; Escobar, C.A.; Ramirez-Tagle, R. Structural antitumoral activity relation-ships of synthetic chalcones. Int. J. Mol. Sci., 2009, 10(1), 221-231.
[http://dx.doi.org/10.3390/ijms10010221] [PMID: 19333443]
(e) Hsieh, C-T.; Hsieh, T-J.; El-Shazly, M.; Chuang, D-W.; Tsai, Y-H.; Yen, C-T.; Wu, S-F.; Wu, Y-C.; Chang, F-R. Synthesis of chalcone derivatives as potential anti-diabetic agents. Bioorg. Med. Chem. Lett., 2012, 22(12), 3912-3915.
[http://dx.doi.org/10.1016/j.bmcl.2012.04.108] [PMID: 22608392]
(f) Singh, P.; Anand, A.; Kumar, V. Recent developments in biological activities of chalcones: A mini review. Eur. J. Med. Chem., 2014, 85, 758-777.
[http://dx.doi.org/10.1016/j.ejmech.2014.08.033] [PMID: 25137491]
(g) Sahu, N.K.; Balbhadra, S.S.; Choudhary, J.; Kohli, D.V. Exploring pharmacological significance of chalcone scaffold: A review. Curr. Med. Chem., 2012, 19(2), 209-225.
[http://dx.doi.org/10.2174/092986712803414132] [PMID: 22320299]
(h) Kuete, V.; Sandjo, L.P. Isobavachalcone: An overview. Chin. J. Integr. Med., 2012, 18(7), 543-547.
[http://dx.doi.org/10.1007/s11655-012-1142-7] [PMID: 22772918]
[65]
Al Zahrani, N.A.; El-Shishtawy, R.M.; Elaasser, M.M.; Asiri, A.M. Synthesis of novel chalcone-based phenothiazine derivatives as antioxidant and anticancer agents. Molecules, 2020, 25, 4566.
[http://dx.doi.org/10.3390/molecules25194566]
[66]
Allen, M.A.; Andrysik, Z.; Dengler, V.L.; Mellert, H.S.; Guarnieri, A.; Freeman, J.A.; Sullivan, K.D.; Galbraith, M.D.; Luo, X.; Kraus, W.L.; Dowell, R.D.; Espinosa, J.M. Global analysis of p53-regulated transcription identifies its direct targets and unexpected regulatory mechanisms. eLife, 2014, 3e02200
[http://dx.doi.org/10.7554/eLife.02200] [PMID: 24867637]
[67]
Gonçalves, B.M.; Salvador, J.A.; Marín, S.; Cascante, M. Synthesis and anticancer activity of novel fluorinated asiatic acid derivatives. Eur. J. Med. Chem., 2016, 114, 101-117.
[http://dx.doi.org/10.1016/j.ejmech.2016.02.057] [PMID: 26974379]
[68]
(a) Zhang, Y.; Su, S.S.; Zhao, S.; Yang, Z.; Zhong, C.-Q.; Chen, X.; Cai, Q.; Yang, Z.-H.; Huang, D.; Wu, R. In situ click chemistry generation of cyclooxygenase-2 inhibitors. Nat. Commun., 2017, 8, 1-14.
[http://dx.doi.org/10.1038/s41467-016-0009-6] [PMID: 28232747]
(b) Czabotar, P.E.; Lessene, G.; Strasser, A.; Adams, J.M. Control of apoptosis by the BCL-2 protein family: Implications for physiology and therapy. Nat. Rev. Mol. Cell Biol., 2014, 15(1), 49-63.
[http://dx.doi.org/10.1038/nrm3722] [PMID: 24355989]
[69]
Prinz, H.; Ridder, A-K.; Vogel, K.; Böhm, K.J.; Ivanov, I.; Ghasemi, J.B.; Aghaee, E.; Müller, K. N-Heterocyclic (4-Phenylpiperazin-1-yl)methanones derived from phenoxazine and phenothiazine as highly potent inhibitors of tubulin polymerization. J. Med. Chem., 2017, 60(2), 749-766.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01591] [PMID: 28045256]
[70]
(a) Mu, J.; Xu, H.; Yang, Y.; Huang, W.; Xiao, J.; Li, M.; Tan, Z.; Ding, Q.; Zhang, L.; Lu, J.; Wu, X.; Liu, Y. Thioridazine, an antipsychotic drug, elicits potent antitumor effects in gastric cancer. Oncol. Rep., 2014, 31(5), 2107-2114.
[http://dx.doi.org/10.3892/or.2014.3068] [PMID: 24604290]
(b) Huang, J.; Zhao, D.; Liu, Z.; Liu, F. Repurposing psychiatric drugs as anti-cancer agents. Cancer Lett., 2018, 419, 257-265.
[http://dx.doi.org/10.1016/j.canlet.2018.01.058] [PMID: 29414306]
[71]
Zhang, Q.; Ding, D.; Zeng, S.X.; Ye, Q-Z.; Lu, H. Structure and activity analysis of Inauhzin analogs as novel antitumor compounds that induce p53 and inhibit cell growth. PLoS One, 2012, 7(10)e46294
[http://dx.doi.org/10.1371/journal.pone.0046294] [PMID: 23115626]
[72]
Vassilev, L.T.; Vu, B.T.; Graves, B.; Carvajal, D.; Podlaski, F.; Filipovic, Z.; Kong, N.; Kammlott, U.; Lukacs, C.; Klein, C.; Fotouhi, N.; Liu, E.A. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science, 2004, 303(5659), 844-848.
[http://dx.doi.org/10.1126/science.1092472] [PMID: 14704432]
[73]
(a) Hemann, M.T.; Lowe, S.W. The p53-Bcl-2 connection. Cell Death Differ., 2006, 13(8), 1256-1259.
[http://dx.doi.org/10.1038/sj.cdd.4401962] [PMID: 16710363]
(b) Antonsson, B.; Montessuit, S.; Sanchez, B.; Martinou, J-C. Bax is present as a high molecular weight oligomer/complex in the mitochondrial membrane of apoptotic cells. J. Biol. Chem., 2001, 276(15), 11615-11623.
[http://dx.doi.org/10.1074/jbc.M010810200] [PMID: 11136736]
(c) Scorrano, L.; Korsmeyer, S.J. Mechanisms of cytochrome c release by proapoptotic BCL-2 family members. Biochem. Biophys. Res. Commun., 2003, 304(3), 437-444.
[http://dx.doi.org/10.1016/S0006-291X(03)00615-6] [PMID: 12729577]
(d) Antonsson, B.; Martinou, J-C. The Bcl-2 protein family. Exp. Cell Res., 2000, 256(1), 50-57.
[http://dx.doi.org/10.1006/excr.2000.4839] [PMID: 10739651]

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