Anti-proliferative, Morphological and Molecular Docking Studies of New Thiophene
Derivatives and their Strategy in Ionic Liquids Immobilized Reactions

Rafat   M.   Mohareb; Sayeed      Mukhtar; Humaira      Parveen; Mahmoud   A.   Abdelaziz; Ensaf   S.   Alwan

doi:10.2174/0118715206262307231122104748

Abstract

Background: A number of research were conducted on the pyran and thiophene derivatives, which were attributed to have a wide range of biological activities, including anti-plasmodial, as well as acting as caspase, hepatitis C and cancer inhibitors.

Objective: The multicomponent reactions of the 5-acetyl-2-amino-4-(phenylamino)-thiophene-3-carbonitrile produced biologically active target molecules like pyran and their fused derivatives. Comparison between regular catalytic multi-component reactions and solvent-free ionic liquids immobilized multicomponent was studied.

Methods: The multicomponent reactions in this work were carried out not only under the reflux conditions using triethylamine as a catalyst but also in solvent-free ionic liquids immobilized magnetic nanoparticles (MNPs) catalysts.

Results: Through this work, thirty-one new compounds were synthesized and characterized and were evaluated toward the six cancer cell lines, namely A549, HT-29, MKN-45, U87MG, and SMMC-7721 and H460. The most active compounds were further screened toward seventeen cancer cell lines classified according to the disease. In addition, the effect of compound 11e on the A549 cell line was selected to make further morphological changes in the cell line. The Molecular docking studies of 11e and 11f were carried and promising results were obtained.

Conclusion: The synthesis of heterocyclic compounds derived from thiophene derivatives has been receiving significant attention. After a detailed optimizing study, it has been found that the solvent-free ionic liquids immobilized multi-component syntheses afforded a high yield of compounds, opening a greener procedure for this synthetically relevant transformation. Many of the synthesized compounds can be considered anticancer agents, enhancing further studies.

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[1]
Ismail, L.A.; Alfaifi, M.Y.; Elbehairi, S.E.I.; Elshaarawy, R.F.M.; Gad, E.M.; El-Sayed, W.N. Hybrid organoruthenium(II) complexes with thiophene-β-diketo-benzazole ligands: Synthesis, optical properties, CT-DNA interactions and anticancer activity. J. Organomet. Chem.,  2021, 949, 121960.
 [http://dx.doi.org/10.1016/j.jorganchem.2021.121960]

[2]
Romagnoli, R.; Preti, D.; Hamel, E.; Bortolozzi, R.; Viola, G.; Brancale, A.; Ferla, S.; Morciano, G.; Pinton, P. Concise synthesis and biological evaluation of 2-Aryl-3-Anilinobenzo[b]thiophene derivatives as potent apoptosis-inducing agents. Bioorg. Chem.,  2021, 112, 104919.
 [http://dx.doi.org/10.1016/j.bioorg.2021.104919] [PMID: 33957538]

[3]
Hollick, J.J.; Golding, B.T.; Hardcastle, I.R.; Martin, N.; Richardson, C.; Rigoreau, L.J.M.; Smith, G.C.M.; Griffin, R.J. 2,6-Disubstituted pyran-4-one and thiopyran-4-one inhibitors of DNA-Dependent protein kinase (DNA-PK). Bioorg. Med. Chem. Lett.,  2003, 13(18), 3083-3086.
 [http://dx.doi.org/10.1016/S0960-894X(03)00652-8] [PMID: 12941339]

[4]
Yadav, N.; Agarwal, D.; Kumar, S.; Dixit, A.K.; Gupta, R.D.; Awasthi, S.K. In vitro antiplasmodial efficacy of synthetic coumarin-triazole analogs. Eur. J. Med. Chem.,  2018, 145, 735-745.
 [http://dx.doi.org/10.1016/j.ejmech.2018.01.017] [PMID: 29366931]

[5]
Ahagh, M.H.; Dehghan, G.; Mehdipour, M.; Teimuri-Mofrad, R.; Payami, E.; Sheibani, N.; Ghaffari, M.; Asadi, M. Synthesis, characterization, anti-proliferative properties and DNA binding of benzochromene derivatives: Increased Bax/Bcl-2 ratio and caspase-dependent apoptosis in colorectal cancer cell line. Bioorg. Chem.,  2019, 93, 103329.
 [http://dx.doi.org/10.1016/j.bioorg.2019.103329] [PMID: 31590040]

[6]
Gopalsamy, A.; Aplasca, A.; Ciszewski, G.; Park, K.; Ellingboe, J.W.; Orlowski, M.; Feld, B.; Howe, A.Y.M. Design and synthesis of 3,4-dihydro-1H-[1]-benzothieno[2,3-c]pyran and 3,4-dihydro-1H-pyrano[3,4-b]benzofuran derivatives as non-nucleoside inhibitors of HCV NS5B RNA dependent RNA polymerase. Bioorg. Med. Chem. Lett.,  2006, 16(2), 457-460.
 [http://dx.doi.org/10.1016/j.bmcl.2005.08.114] [PMID: 16274990]

[7]
Chen, Y.L.; Tang, J.; Kesler, M.J.; Sham, Y.Y.; Vince, R.; Geraghty, R.J.; Wang, Z. The design, synthesis and biological evaluations of C-6 or C-7 substituted 2-hydroxyisoquinoline-1,3-diones as inhibitors of hepatitis C virus. Bioorg. Med. Chem.,  2012, 20(1), 467-479.
 [http://dx.doi.org/10.1016/j.bmc.2011.10.058] [PMID: 22100256]

[8]
Dong, Y.; Shi, Q.; Nakagawa-Goto, K.; Wu, P.C.; Morris-Natschke, S.L.; Brossi, A.; Bastow, K.F.; Lang, J.Y.; Hung, M.C.; Lee, K.H. Antitumor agents 270. Novel substituted 6-phenyl-4H-furo[3,2-c]pyran-4-one derivatives as potent and highly selective anti-breast cancer agents. Bioorg. Med. Chem.,  2010, 18(2), 803-808.
 [http://dx.doi.org/10.1016/j.bmc.2009.11.049] [PMID: 20034799]

[9]
Parthasarathy, K.; Praveen, C.; Balachandran, C.; Senthil, K, P.; Ignacimuthu, S.; Perumal, P.T. Cu(OTf)2 catalyzed three component reaction: Efficient synthesis of spiro[indoline-3,4′-pyrano[3,2-b]pyran derivatives and their anticancer potency towards A549 human lung cancer cell lines. Bioorg. Med. Chem. Lett.,  2013, 23(9), 2708-2713.
 [http://dx.doi.org/10.1016/j.bmcl.2013.02.086] [PMID: 23522833]

[10]
Elyasi, Z.; Ghomi, J.S.; Najafi, G.R. Ultrasound-Engineered fabrication of immobilized molybdenum complex on Cross-Linked poly (Ionic Liquid) as a new acidic catalyst for the regioselective synthesis of pharmaceutical polysubstituted spiro compounds. Ultrason. Sonochem.,  2021, 75, 105614.
 [http://dx.doi.org/10.1016/j.ultsonch.2021.105614] [PMID: 34111724]

[11]
Hernández, E.; Santiago, R.; Moya, C.; Navarro, P.; Palomar, J. Understanding the CO2 valorization to propylene carbonate catalyzed by 1-butyl-3-methylimidazolium amino acid ionic liquids. J. Mol. Liq.,  2021, 324, 114782.
 [http://dx.doi.org/10.1016/j.molliq.2020.114782]

[12]
Wang, L.; Li, C.; Wang, N.; Li, K.; Chen, X.; Yu, X-Q. Enzyme-mediated domino synthesis of 2-alkylbenzimidazoles in solvent-free system: A green route to heterocyclic compound. J. Mol. Catal., B Enzym.,  2010, 67(1-2), 16-20.
 [http://dx.doi.org/10.1016/j.molcatb.2010.06.013]

[13]
Kumar, D.; Prakasham, A.P.; Gangwar, M.K.; Ghosh, P. Solvent-free cyanosilylation of aromatic and heteroaryl aldehydes catalyzed by a cationic iron N-heterocyclic carbene complex at ambient temperature under UV irradiation. Inorg. Chim. Acta,  2019, 495, 119003.
 [http://dx.doi.org/10.1016/j.ica.2019.119003]

[14]
Feroci, M.; Elinson, M.N.; Rossi, L.; Inesi, A. The double role of ionic liquids in organic electrosynthesis: Precursors of N-heterocyclic carbenes and green solvents. Henry reaction. Electrochem. Commun.,  2009, 11(7), 1523-1526.
 [http://dx.doi.org/10.1016/j.elecom.2009.05.045]

[15]
Elkhidr, H.E.; Ertekin, Z.; Udum, Y.A.; Pekmez, K. Electrosynthesis and characterizations of electrochromic and soluble polymer films based on N- substituted carbazole derivates. Synth. Met.,  2020, 260, 116253.
 [http://dx.doi.org/10.1016/j.synthmet.2019.116253]

[16]
Hu, K.; Niyazymbetov, M.E.; Evans, D.H. Nucleophilic aromatic substitution by paired electrosynthesis: Reactions of methoxy arenes with 1H-tetrazoles. Tetrahedron Lett.,  1995, 36(39), 7027-7030.
 [http://dx.doi.org/10.1016/0040-4039(95)01455-Q]

[17]
Ramesh, K.; Satyanarayana, G. Propargyl alcohols as alkyne sources: Synthesis of heterocyclic compounds under microwave irradiation. J. Organomet. Chem.,  2020, 922, 121350.
 [http://dx.doi.org/10.1016/j.jorganchem.2020.121350]

[18]
Khan, S.A.; Asiri, A.M.; Al-Ghamdi, N.S.M.; Asad, M.; Zayed, M.E.M.; Elroby, S.A.K.; Aqlan, F.M.; Wani, M.Y.; Sharma, K. Microwave assisted synthesis of chalcone and its polycyclic heterocyclic analogues as promising antibacterial agents: In vitro, in silico and DFT studies. J. Mol. Struct.,  2019, 1190, 77-85.
 [http://dx.doi.org/10.1016/j.molstruc.2019.04.046]

[19]
Kurva, M.; Pharande, S.G.; Quezada-Soto, A.; Gámez-Montaño, R. Ultrasound assisted green synthesis of bound type bis-heterocyclic carbazolyl imidazo[1,2-a]pyridines via Groebke-Blackburn-Bienayme reaction. Tetrahedron Lett.,  2018, 59(16), 1596-1599.
 [http://dx.doi.org/10.1016/j.tetlet.2018.03.031]

[20]
Mosslemin, M.H.; Nateghi, M.R. Rapid and efficient synthesis of fused heterocyclic pyrimidines under ultrasonic irradiation. Ultrason. Sonochem.,  2010, 17(1), 162-167.
 [http://dx.doi.org/10.1016/j.ultsonch.2009.07.002] [PMID: 19679502]

[21]
Mojtahedi, M.M.; Abaee, M.S.; Samianifard, M.; Shamloo, A.; Padyab, M.; Mesbah, A.W.; Harms, K. Ultrasound mediation for efficient synthesis of monoarylidene derivatives of homo- and heterocyclic ketones. Ultrason. Sonochem.,  2013, 20(3), 924-930.
 [http://dx.doi.org/10.1016/j.ultsonch.2012.11.004] [PMID: 23219616]

[22]
Talha, A.; Tachallait, H.; Benhida, R.; Bougrin, K. Green one-pot four-component synthesis of 3,5-disubstituted isoxazoles- sulfonates and sulfonamides using a combination of NaDCC as metal-free catalyst and ultrasonic activation in water. Tetrahedron Lett.,  2021, 81, 153366.
 [http://dx.doi.org/10.1016/j.tetlet.2021.153366]

[23]
Maddila, S.N.; Maddila, S.; Khumalo, M.; Bhaskaruni, S.V.H.S.; Jonnalagadda, S.B. An eco-friendly approach for synthesis of novel substituted 4H-chromenes in aqueous ethanol under ultra-sonication with 94% atom economy. J. Mol. Struct.,  2019, 1185, 357-360.
 [http://dx.doi.org/10.1016/j.molstruc.2019.03.006]

[24]
Achary, L.S.K.; Nayak, P.S.; Barik, B.; Kumar, A.; Dash, P. Ultrasonic-assisted green synthesis of β-amino carbonyl compounds by copper oxide nanoparticles decorated phosphate functionalized graphene oxide via Mannich reaction. Catal. Today,  2020, 348, 137-147.
 [http://dx.doi.org/10.1016/j.cattod.2019.07.050]

[25]
Govindaraju, S.; Tabassum, S. Sulphuric acid supported silica gel (H2SO4-SiO2) as an efficient catalyst for one-pot multicomponent synthesis of pyrano[2,3-c]pyrazol-amines under ultrasonication. Mater. Today Proc.,  2021, 45, 3762-3768.
 [http://dx.doi.org/10.1016/j.matpr.2021.01.273]

[26]
Devi, L.; Robert, A.R.; Ganja, H.; Maddila, S.; Jonnalagadda, S.B. A rapid, sustainable and environmental friendly protocol for the catalyst-free synthesis of 2-methyl-5-oxo-hexahydroquinoline-3-carboxylate via ultrasonic irradiation. Chem. Data Collect.,  2020, 28, 100432.
 [http://dx.doi.org/10.1016/j.cdc.2020.100432]

[27]
Karimi-Maleh, H.; Darabi, R.; Shabani-Nooshabadi, M.; Baghayeri, M.; Karimi, F.; Rouhi, J.; Alizadeh, M.; Karaman, O.; Vasseghian, Y.; Karaman, C. Determination of D&C red 33 and patent blue V azo dyes using an impressive electrochemical sensor based on carbon paste electrode modified with ZIF-8/g-C3N4/Co and ionic liquid in mouthwash and toothpaste as real samples. Food Chem. Toxicol.,  2022, 162, 112907.
 [http://dx.doi.org/10.1016/j.fct.2022.112907] [PMID: 35271984]

[28]
Karimi-Maleh, H.; Ranjbari, S.; Tanhaei, B.; Ayati, A.; Orooji, Y.; Alizadeh, M.; Karimi, F.; Salmanpour, S.; Rouhi, J.; Sillanpää, M.; Sen, F. Novel 1-butyl-3-methylimidazolium bromide impregnated chitosan hydrogel beads nanostructure as an efficient nanobio-adsorbent for cationic dye removal: Kinetic study. Environ. Res.,  2021, 195, 110809.
 [http://dx.doi.org/10.1016/j.envres.2021.110809] [PMID: 33515581]

[29]
Karimi-Maleh, H.; Karimi, F.; Malekmohammadi, S.; Zakariae, N.; Esmaeili, R.; Rostamnia, S.; Yola, M.L.; Atar, N.; Movaghgharnezhad, S.; Rajendran, S.; Razmjou, A.; Orooji, Y.; Agarwal, S.; Gupta, V.K. An amplified voltammetric sensor based on platinum nanoparticle/polyoxometalate/two-dimensional hexagonal boron nitride nanosheets composite and ionic liquid for determination of N-hydroxysuccinimide in water samples. J. Mol. Liq.,  2020, 310, 113185.
 [http://dx.doi.org/10.1016/j.molliq.2020.113185]

[30]
Sanati, A.L.; Faridbod, F.; Ganjali, M.R. Synergic effect of graphene quantum dots and room temperature ionic liquid for the fabrication of highly sensitive voltammetric sensor for levodopa determination in the presence of serotonin. J. Mol. Liq.,  2017, 241, 316-320.
 [http://dx.doi.org/10.1016/j.molliq.2017.04.123]

[31]
Capito, R.M.; Azevedo, H.S.; Velichko, Y.S.; Mata, A.; Stupp, S.I. Self-assembly of large and small molecules into hierarchically ordered sacs and membranes. Science,  2008, 319(5871), 1812-1816.
 [http://dx.doi.org/10.1126/science.1154586] [PMID: 18369143]

[32]
Willerich, I.; Gröhn, F. Photoswitchable nanoassemblies by electrostatic self-assembly. Angew. Chem. Int. Ed.,  2010, 49(44), 8104-8108.
 [http://dx.doi.org/10.1002/anie.201003271] [PMID: 20799308]

[33]
Goel, A.; Ram, V.J. Natural and synthetic 2H-pyran-2-ones and their versatility in organic synthesis. Tetrahedron,  2009, 65(38), 7865-7913.
 [http://dx.doi.org/10.1016/j.tet.2009.06.031]

[34]
Dwivedi, G.R.; Rai, R.; Pratap, R.; Singh, K.; Pati, S.; Sahu, S.N.; Kant, R.; Darokar, M.P.; Yadav, D.K. Drug resistance reversal potential of multifunctional thieno[3,2-c]pyran via potentiation of antibiotics in MDR P. aeruginosa. Biomed. Pharmacother.,  2021, 142, 112084.
 [http://dx.doi.org/10.1016/j.biopha.2021.112084] [PMID: 34449308]

[35]
Banerjee, S.; Horn, A.; Khatri, H.; Sereda, G. A green one-pot multicomponent synthesis of 4H-pyrans and polysubstituted aniline derivatives of biological, pharmacological, and optical applications using silica nanoparticles as reusable catalyst. Tetrahedron Lett.,  2011, 52(16), 1878-1881.
 [http://dx.doi.org/10.1016/j.tetlet.2011.02.031]

[36]
Kumar, D.; Reddy, V.B.; Sharad, S.; Dube, U.; Kapur, S. A facile one-pot green synthesis and antibacterial activity of 2-amino-4H-pyrans and 2-amino-5-oxo-5,6,7,8-tetrahydro-4H-chromenes. Eur. J. Med. Chem.,  2009, 44(9), 3805-3809.
 [http://dx.doi.org/10.1016/j.ejmech.2009.04.017] [PMID: 19419801]

[37]
El-Sayed, N.N.E.; Abdelaziz, M.A.; Wardakhan, W.W.; Mohareb, R.M. The Knoevenagel reaction of cyanoacetylhydrazine with pregnenolone: Synthesis of thiophene, thieno[2,3-d]pyrimidine, 1,2,4-triazole, pyran and pyridine derivatives with anti-inflammatory and anti-ulcer activities. Steroids,  2016, 107, 98-111.
 [http://dx.doi.org/10.1016/j.steroids.2015.12.023] [PMID: 26772772]

[38]
Wang, D.C.; Xie, Y.M.; Fan, C.; Yao, S.; Song, H. Efficient and mild cyclization procedures for the synthesis of novel 2-amino-4H-pyran derivatives with potential antitumor activity. Chin. Chem. Lett.,  2014, 25(7), 1011-1013.
 [http://dx.doi.org/10.1016/j.cclet.2014.04.026]

[39]
Dong, Y.; Nakagawa-Goto, K.; Lai, C.Y.; Morris-Natschke, S.L.; Bastow, K.F.; Lee, K.H. Antitumor agents 287. Substituted 4-amino-2H-pyran-2-one (APO) analogs reveal a new scaffold from neo-tanshinlactone with in vitro anticancer activity. Bioorg. Med. Chem. Lett.,  2011, 21(8), 2341-2344.
 [http://dx.doi.org/10.1016/j.bmcl.2011.02.084] [PMID: 21420855]

[40]
Pandey, J.; Jha, A.K.; Hajela, K. Synthesis and biological activities of some new dibenzopyranones and dibenzopyrans: search for potential oestrogen receptor agonists and antagonists. Bioorg. Med. Chem.,  2004, 12(9), 2239-2249.
 [http://dx.doi.org/10.1016/j.bmc.2004.02.018] [PMID: 15080923]

[41]
Ramkumar, K.; Tambov, K.V.; Gundla, R.; Manaev, A.V.; Yarovenko, V.; Traven, V.F.; Neamati, N. Discovery of 3-acetyl-4-hydroxy-2-pyranone derivatives and their difluoridoborate complexes as a novel class of HIV-1 integrase Inhibitors. Bioorg. Med. Chem.,  2008, 16(19), 8988-8998.
 [http://dx.doi.org/10.1016/j.bmc.2008.08.067] [PMID: 18805696]

[42]
Hu, C.; Jiang, L.; Tang, L.; Zhang, M.; Sheng, R. Design, synthesis and biological evaluation of 2-styryl-5-hydroxy-4-pyrone derivatives and analogues as multiple functional agents with the potential for the treatment of Alzheimer’s disease. Bioorg. Med. Chem.,  2021, 44, 116306.
 [http://dx.doi.org/10.1016/j.bmc.2021.116306] [PMID: 34274550]

[43]
Bedair, A.H.; Emam, H.A.; El-Hady, N.A.; Ahmed, K.A.R.; El-Agrody, A.M. Synthesis and antimicrobial activities of novel naphtho[2,1-b]pyran, pyrano[2,3-d]pyrimidine and pyrano[3,2-e][1,2,4]triazolo[2,3-c]-pyrimidine derivatives. Farmaco,  2001, 56(12), 965-973.
 [http://dx.doi.org/10.1016/S0014-827X(01)01168-5] [PMID: 11829118]

[44]
Goli-Jolodar, O.; Shirini, F.; Seddighi, M. An efficient and practical synthesis of specially 2-amino-4H-pyrans catalyzed by C4(DABCO-SO3H)2·4Cl. Dyes Pigments,  2016, 133, 292-303.
 [http://dx.doi.org/10.1016/j.dyepig.2016.06.001]

[45]
Muraoka, K.; Nagao, H.; Hori, T.; Sakaya, S.; Hoshino, T.; Miyao, Y.; Murai, T.; Edanaga, M.; Nakanishi, M. Antihypertensive effect and its mechanism of action of a new benzopyran derivative, KP-403. Jpn. J. Pharmacol.,  1991, 55, 341.
 [http://dx.doi.org/10.1016/S0021-5198(19)39411-9]

[46]
Yang, Z.J.; Gong, Q.T.; Wang, Y.; Yu, Y.; Liu, Y.H.; Wang, N.; Yu, X.Q. Biocatalytic tandem multicomponent reactions for one-pot synthesis of 2-Amino-4H-Pyran library and in vitro biological evaluation. Mol. Catalysis,  2020, 491, 110983.
 [http://dx.doi.org/10.1016/j.mcat.2020.110983]

[47]
Milyutin, C.V.; Lichitsky, B.V.; Melekhina, V.G.; Komogortsev, A.N.; Fakhrutdinov, A.N.; Minyaev, M.E.; Krayushkin, M.M. Synthesis of 1H-pyrano[4,3-b]benzofuran-1-one derivatives via photochemical cyclization of substituted 4H-furo[3,2-c]pyran-4-ones. Tetrahedron Lett.,  2020, 61(44), 152469.
 [http://dx.doi.org/10.1016/j.tetlet.2020.152469]

[48]
Mirgane, N.; Kotwal, S.; Karnik, A. Ionic liquid promoted diels-alder reaction between anthrone and maleimides. Open Chem.,  2010, 8(2), 356-360.
 [http://dx.doi.org/10.2478/s11532-009-0136-6]

[49]
Mirgane, N.A.; Akhtar, M.H.; Karnik, A.V. Chiral ionic liquid mediated Diels-Alder reaction between anthrone enolate and maleimides. Lett. Org. Chem.,  2010, 7, 343-347.
 [http://dx.doi.org/10.2174/157017810791130559]

[50]
Roy, P.T.; Mirgane, A.A. Ionic Liquid: A versatile green catalyst for the reaction of 9-hydroxymethylanthracenes with maleimides under solvent-free conditions. Indian J. Heterocycl. Chem.,  2021, 31, 295-299.

[51]
Liu, L.; Siegmund, A.; Xi, N.; Kaplan-Lefko, P.; Rex, K.; Chen, A.; Lin, J.; Moriguchi, J.; Berry, L.; Huang, L.; Teffera, Y.; Yang, Y.; Zhang, Y.; Bellon, S.F.; Lee, M.; Shimanovich, R.; Bak, A.; Dominguez, C.; Norman, M.H.; Harmange, J.C.; Dussault, I.; Kim, T.S. Discovery of a potent, selective, and orally bioavailable c-met inhibitor: 1-(2-Hydroxy-2-methylpropyl)- N -(5-(7-methoxyquinolin-4-yloxy)pyridin-2-yl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1 H -pyrazole-4-carboxamide (AMG 458). J. Med. Chem.,  2008, 51(13), 3688-3691.
 [http://dx.doi.org/10.1021/jm800401t] [PMID: 18553959]

[52]
Mohareb, R.M.; Wardakhan, W.W.; Hamed, F.I. Synthesis and cytotoxicity of fused thiophene and pyrazole derivatives derived from 2-N-acetyl-3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene. Med. Chem. Res.,  2015, 24(5), 2043-2054.
 [http://dx.doi.org/10.1007/s00044-014-1273-9]

[53]
Mohareb, R.M.; Zaki, M.Y.; Abbas, N.S. Synthesis, anti-inflammatory and anti-ulcer evaluations of thiazole, thiophene, pyridine and pyran derivatives derived from androstenedione. Steroids,  2015, 98, 80-91.
 [http://dx.doi.org/10.1016/j.steroids.2015.03.001] [PMID: 25759119]

[54]
Peach, M.L.; Tan, N.; Choyke, S.J.; Giubellino, A.; Athauda, G.; Burke, T.R., Jr; Nicklaus, M.C.; Bottaro, D.P.; Bottaro, D.P. Directed discovery of agents targeting the Met tyrosine kinase domain by virtual screening. J. Med. Chem.,  2009, 52(4), 943-951.
 [http://dx.doi.org/10.1021/jm800791f] [PMID: 19199650]

[55]
Bacco, F.D.; Luraghi, P.; Medico, E.; Reato, G.; Girolami, F.; Perera, T.; Gabriele, P.; Comoglio, P.M.; Boccaccio, C. Induction of MET by ionizing radiation and its role in radioresistance and invasive growth of cancer. J. Natl. Cancer Inst.,  2011, 103, 645-661.
 [http://dx.doi.org/10.1093/jnci/djr093] [PMID: 21464397]

[56]
Knudsen, B.S.; Gmyrek, G.A.; Inra, J.; Scherr, D.S.; Vaughan, E.D.; Nanus, D.M.; Kattan, M.W.; Gerald, W.L.; Vande, W, G.F. High expression of the Met receptor in prostate cancer metastasis to bone. Urology,  2002, 60(6), 1113-1117.
 [http://dx.doi.org/10.1016/S0090-4295(02)01954-4] [PMID: 12475693]

[57]
Humphrey, P.A.; Zhu, X.; Zarnegar, R.; Swanson, P.E.; Ratliff, T.L.; Vollmer, R.T.; Day, M.L. Hepatocyte growth factor and its receptor (c-MET) in prostatic carcinoma. Am. J. Pathol.,  1995, 147(2), 386-396.
 [PMID: 7639332]

[58]
Rubin, J.; Bottaro, D.P.; Aaronson, S.A. Hepatocyte growth factor/scatter factor and its receptor, the c-met proto-oncogene product. Biochim. Biophys. Acta Rev. Cancer,  1993, 1155(3), 357-371.
 [http://dx.doi.org/10.1016/0304-419X(93)90015-5] [PMID: 8268192]

[59]
Organ, S.L.; Tsao, M.S. An overview of the c-MET signaling pathway. Ther. Adv. Med. Oncol.,  2011, 3(S1), S7-S19.
 [http://dx.doi.org/10.1177/1758834011422556] [PMID: 22128289]

[60]
Jeffers, M.; Rong, S.; Vande Woude, G.F. Hepatocyte growth factor/scatter factor—Met signaling in tumorigenicity and invasion/metastasis. J. Mol. Med.,  1996, 74(9), 505-513.
 [http://dx.doi.org/10.1007/BF00204976] [PMID: 8892055]

[61]
Verras, M.; Lee, J.; Xue, H.; Li, T.H.; Wang, Y.; Sun, Z. The androgen receptor negatively regulates the expression of c-Met: implications for a novel mechanism of prostate cancer progression. Cancer Res.,  2007, 67(3), 967-975.
 [http://dx.doi.org/10.1158/0008-5472.CAN-06-3552] [PMID: 17283128]

[62]
Li, S.; Zhao, Y.; Wang, K.; Gao, Y.; Han, J.; Cui, B.; Gong, P. Discovery of novel 4-(2-fluorophenoxy)quinoline derivatives bearing 4-oxo-1,4-dihydrocinnoline-3-carboxamide moiety as c-Met kinase inhibitors. Bioorg. Med. Chem.,  2013, 21(11), 2843-2855.
 [http://dx.doi.org/10.1016/j.bmc.2013.04.013] [PMID: 23628470]

[63]
Zhu, W.; Wang, W.; Xu, S.; Wang, J.; Tang, Q.; Wu, C.; Zhao, Y.; Zheng, P. Synthesis, and docking studies of phenylpyrimidine-carboxamide derivatives bearing 1H-pyrrolo[2,3-b]pyridine moiety as c-Met inhibitors. Bioorg. Med. Chem.,  2016, 24(8), 1749-1756.
 [http://dx.doi.org/10.1016/j.bmc.2016.02.046] [PMID: 26964675]

[64]
Mohareb, R.M.; Abdallah, A.E.M.; Abdelaziz, M.A. New approaches for the synthesis of pyrazole, thiophene, thieno[2,3-b]pyridine, and thiazole derivatives together with their anti-tumor evaluations. Med. Chem. Res.,  2014, 23(2), 564-579.
 [http://dx.doi.org/10.1007/s00044-013-0664-7]

[65]
Sherif, S.M.; Abdel-Sayed, N.I.; El-Kousy, S.M.; Mohareb, R.M. The reaction of carbon disulfide with diethyl 3-amino-2-cyano-2-penten-1,5-dicarboxylate: A convenient synthesis of polyfunctionally substituted thiophenes and their fused derivatives. Monatsh. Chem.,  1995, 126(5), 601-608.
 [http://dx.doi.org/10.1007/BF00807435]

[66]
Zohdi, H.Z.; Mohareb, R.M.; Wardakhan, W.W. Heterocyclic synthesis with isothiocyanate and sulfur: A novel synthesis of pyrido[2,3-d]thiazole, thiazolo[4′,5′:2,3]Pyridino[4,5-d]pyridazine and thiazolo[4,5-b]isoquinoline derivatives. Phosphorous Sulfur& Silicon,  1995, 101, 179-187.
 [http://dx.doi.org/10.1080/10426509508042515]

[67]
Mohareb, R.M.; Sherif, S.M.; Sami, A.M. Thiophenylhydrazonoacetates in heterocyclic synthesis. Phosphorous Sulfur & Silicon,  1995, 101, 57-65.
 [http://dx.doi.org/10.1080/10426509508042499]

[68]
Azgomi, A.; Mokhtary, M. Nano-Fe3O4@SiO2 supported ionic liquid as an efficient catalyst for the synthesis of 1,3-thiazolidin-4-ones under solvent-free conditions. Mol. Catal.,  398, 58-64.
 [http://dx.doi.org/10.1016/j.molcata.2014.11.018]

[69]
Boyd, M.R.; Paull, K.D. Some practical considerations and applications of the national cancer institute in vitro anticancer drug discovery screen. Drug Dev. Res.,  1995, 34(2), 91-109.
 [http://dx.doi.org/10.1002/ddr.430340203]

[70]
Boyd, M.R. Cancer Drug Discovery and Development, 2; Teicher, B.A., Ed.; Humana Press, 1997, pp. 23-43.

[71]
Han, X.; Alu, A.; Liu, H.; Shi, Y.; Wei, X.; Cai, L.; Wei, Y. Biomaterial-assisted biotherapy: A brief review of biomaterials used in drug delivery, vaccine development, gene therapy, and stem cell therapy. Bioact. Mater.,  2022, 17, 29-48.
 [http://dx.doi.org/10.1016/j.bioactmat.2022.01.011] [PMID: 35386442]

[72]
Mendieta, I.; Rodríguez-Nieto, M.; Nuñez-Anita, R.E.; Menchaca-Arredondo, J.L.; García-Alcocer, G.; Berumen, L.C.; Berumen, L.C. Ultrastructural changes associated to the neuroendocrine transdifferentiation of the lung adenocarcinoma cell line A549. Acta Histochem.,  2021, 123(8), 151797.
 [http://dx.doi.org/10.1016/j.acthis.2021.151797] [PMID: 34688180]

[73]
Gao, J.; Zhao, Y.; Wang, C.; Ji, H.; Yu, J.; Liu, C.; Liu, A. A novel synthetic chitosan selenate (CS) induces apoptosis in A549 lung cancer cells via the Fas/FasL pathway. Int. J. Biol. Macromol.,  2020, 158, 689-697.
 [http://dx.doi.org/10.1016/j.ijbiomac.2020.05.016] [PMID: 32387597]

[74]
Nunhart, P.; Konkoľová, E.; Janovec, L.; Jendželovský, R.; Vargová, J.; Ševc, J.; Matejová, M.; Miltáková, B.; Fedoročko, P.; Kozurkova, M. Fluorinated 3,6,9-trisubstituted acridine derivatives as DNA interacting agents and topoisomerase inhibitors with A549 antiproliferative activity. Bioorg. Chem.,  2020, 94, 103393.
 [http://dx.doi.org/10.1016/j.bioorg.2019.103393] [PMID: 31679839]

[75]
Garofalo, S.; Rosa, R.; Bianco, R.; Tortora, G. EGFR-targeting agents in oncology. Expert Opin. Ther. Pat.,  2008, 18(8), 889-901.
 [http://dx.doi.org/10.1517/13543776.18.8.889]

[76]
Al-Suwaidan, I.A.; Abdel-Aziz, N.I.; El-Azab, A.S.; El-Sayed, M.A.A.; Alanazi, A.M.; El-Ashmawy, M.B.; Abdel-Aziz, A.A.M. Antitumor evaluation and molecular docking study of substituted 2-benzylidenebutane-1,3-dione, 2-hydrazonobutane-1,3-dione and trifluoromethyl-1H-pyrazole analogues. J. Enzyme Inhib. Med. Chem.,  2015, 30(4), 679-687.
 [http://dx.doi.org/10.3109/14756366.2014.960863] [PMID: 25472776]

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DOI https://dx.doi.org/10.2174/0118715206262307231122104748	Print ISSN 1871-5206
Publisher Name Bentham Science Publisher	Online ISSN 1875-5992

Anti-Cancer Agents in Medicinal Chemistry

Anti-proliferative, Morphological and Molecular Docking Studies of New Thiophene Derivatives and their Strategy in Ionic Liquids Immobilized Reactions

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