Login Register Cart 0
Generic placeholder image

Mini-Reviews in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Synthesis, Cytotoxicity and Docking Simulation of Novel Annulated Dihydroisoquinoline Heterocycles

Author(s): Fatma M. Saleh, Hamdi M. Hassaneen*, Magda F. Mohamed and Yasmin Sh. Mohamed

Volume 20, Issue 12, 2020

Page: [1166 - 1178] Pages: 13

DOI: 10.2174/1389557520666200130104632

Price: $65

Abstract

Objective: Coupling of ethyl 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)acetate 2 with diazotized anilines in ethanol in the presence of sodium acetate yielded 2-(2-arylhydrazono)-2-(6,7- dimethoxy-3,4-dihydroisoquinolin-1-yl)acetate (4a-f).

Methods: Treatment of 2 with α-bromoketones 6a-f in dry benzene at reflux gave the corresponding isoquinolinium bromides 7a-f. Refluxing of each of the salts 7a-f in dry benzene and in the presence of triethylamine yielded 2-arylpyrrolo-[2,1-a]isoquinoline structures 8a-f, that converted to ethyl (E)-8,9- dimethoxy-3-(phenyldiazen-yl)-2-(aryl)-5,6-dihydropyrrolo[2,1-a]isoquinoline-1-carboxylate (9a-f) upon treatment with diazotized anilines 3 in ethanol in the presence of sodium acetate.

Results and Conclusion: Cytotoxic assay was performed for in vitro antitumor screening against caucasian breast adenocarcinoma (MCF7), hepatocellular carcinoma (HepG2) and colorectal carcinoma (HCT-116) cell lines. The results were compared with the standard anticancer drug (doxorubicin). Molecular docking using MOE 2014.09 software was carried out for the most potent compound 4d, which showed the highest binding affinity towards the four tested proteins and thus initiated apoptosis of cancer cells.

Keywords: Fused isoquinoline, diazotized anilines, α-bromoketones, antitumor screening, molecular docking, HepG2.

« Previous Next »
Graphical Abstract

[1]
Rueffer, M.; Amann, M.; Zenk, M.H. S-Adenosyl-L-methionine: Columbamine-O-methyl transferase, a compartmentalized enzyme in protoberberine biosynthesis. Plant Cell Rep., 1986, 5(3), 182-185.
[http://dx.doi.org/10.1007/BF00269113] [PMID: 24248127]
[2]
Galat, A. Synthesis of papaverine and some related compounds. J. Am. Chem. Soc., 1951, 73(8), 3654-3656.
[http://dx.doi.org/10.1021/ja01152a027]
[3]
Huang, L.; Shi, A.; He, F.; Li, X. Synthesis, biological evaluation, and molecular modeling of berberine derivatives as potent acetylcholinesterase inhibitors. Bioorg. Med. Chem., 2010, 18(3), 1244-1251.
[http://dx.doi.org/10.1016/j.bmc.2009.12.035] [PMID: 20056426]
[4]
Barbosa-Filho, J.M.; Piuvezam, M.R.; Moura, M.D.; Silva, M.S.; Lima, K.V.B.; da-Cunha, E.V.L.; Fechine, I.M.; Takemura, O.S. Anti-inflammatory activity of alkaloids: A twenty-century review. Rev. Bras. Farmacogn., 2006, 16(1), 109-139.
[http://dx.doi.org/10.1590/S0102-695X2006000100020]
[5]
Elwan, N.M.; Abdelhadi, H.A.; Abdallah, T.A.; Hassaneen, H.M. Synthesis of [1,2,4]triazolo[3,4-a]isoquinolines and pyrrolo[2,1-a]isoquinolines using α-keto hydrazonoyl halides. Tetrahedron, 1996, 52(10), 3451-3456.
[http://dx.doi.org/10.1016/0040-4020(96)00024-5]
[6]
Küpeli, E.; Koşar, M.; Yeşilada, E.; Hüsnü, K.; Başer, C. A comparative study on the anti-inflammatory, antinociceptive and antipyretic effects of isoquinoline alkaloids from the roots of Turkish Berberis species. Life Sci., 2002, 72(6), 645-657.
[http://dx.doi.org/10.1016/S0024-3205(02)02200-2] [PMID: 12467905]
[7]
Whitehouse, M.W.; Fairlie, D.P.; Thong, Y.H. Anti-inflammatory activity of the isoquinoline alkaloid, tetrandrine, against established adjuvant arthritis in rats. Agents Actions, 1994, 42(3-4), 123-127.
[http://dx.doi.org/10.1007/BF01983477] [PMID: 7879697]
[8]
Souto, A.L.; Tavares, J.F.; da Silva, M.S.; Diniz, Mde.F.; de Athayde-Filho, P.F.; Barbosa Filho, J.M. Anti-inflammatory activity of alkaloids: an update from 2000 to 2010. Molecules, 2011, 16(10), 8515-8534.
[http://dx.doi.org/10.3390/molecules16108515] [PMID: 21989312]
[9]
Mukherjee, A.; Dutta, S.; Shanmugavel, M.; Mondhe, D.M.; Sharma, P.R.; Singh, S.K.; Saxena, A.K.; Sanyal, U. 6-Nitro-2-(3-hydroxypropyl)-1H-benz[de]isoquinoline-1,3-dione, a potent antitumor agent, induces cell cycle arrest and apoptosis. J. Exp. Clin. Cancer Res., 2010, 29(1), 175.
[http://dx.doi.org/10.1186/1756-9966-29-175] [PMID: 21194464]
[10]
Knölker, H-J.; Agarwal, S. Total synthesis of the antitumor active pyrrolo[2,1-A]isoquinoline Alkaloid (±)-Crispine A. Tetrahedron Lett., 2005, 46(7), 1173-1175.
[http://dx.doi.org/10.1016/j.tetlet.2004.12.066]
[11]
Mohamed, M.F.; Hassaneen, H.M.; Abdelhamid, I.A. Cytotoxicity, molecular modeling, cell cycle arrest, and apoptotic induction induced by novel tetrahydro-[1,2,4]triazolo[3,4-a]isoquinoline chalcones. Eur. J. Med. Chem., 2018, 143(1), 532-541.
[http://dx.doi.org/10.1016/j.ejmech.2017.11.045] [PMID: 29207336]
[12]
Yang, X.; Yang, S.; Chai, H.; Yang, Z.; Lee, R.J.; Liao, W.; Teng, L. A Novel Isoquinoline Derivative Anticancer Agent and Its Targeted Delivery to Tumor Cells Using Transferrin-Conjugated Liposomes. PLoS One, 2015, 10(8) e0136649
[http://dx.doi.org/10.1371/journal.pone.0136649] [PMID: 26309138]
[13]
Cheon, S.H.; Park, J.S.; Lee, J.Y.; Lee, Y.N.; Yi, H.; Chung, B-H.; Choi, B-G.; Cho, W-J.; Choi, S-U.; Lee, C-O. Structure-activity relationship studies of isoquinolinone type anticancer agent. Arch. Pharm. Res., 2001, 24(4), 276-280.
[http://dx.doi.org/10.1007/BF02975091] [PMID: 11534756]
[14]
Maryanoff, B.E.; McComsey, D.F.; Castanzo, M.J.; Setler, P.E.; Gardocki, J.F.; Shank, R.P.; Schneider, C.R. Pyrroloisoquinoline antidepressants. Potent, enantioselective inhibition of tetrabenazine-induced ptosis and neuronal uptake of norepinephrine, dopamine, and serotonin. J. Med. Chem., 1984, 27(8), 943-946.
[http://dx.doi.org/10.1021/jm00374a001] [PMID: 6747993]
[15]
Buchanan, M.S.; Davis, R.A.; Duffy, S.; Avery, V.M.; Quinn, R.J. Antimalarial benzylisoquinoline alkaloid from the rainforest tree Doryphora sassafras. J. Nat. Prod., 2009, 72(8), 1541-1543.
[http://dx.doi.org/10.1021/np9002564] [PMID: 19637893]
[16]
Kashiwada, Y.; Aoshima, A.; Ikeshiro, Y.; Chen, Y-P.; Furukawa, H.; Itoigawa, M.; Fujioka, T.; Mihashi, K.; Cosentino, L.M.; Morris-Natschke, S.L.; Lee, K.H. Anti-HIV benzylisoquinoline alkaloids and flavonoids from the leaves of Nelumbo nucifera, and structure-activity correlations with related alkaloids. Bioorg. Med. Chem., 2005, 13(2), 443-448.
[http://dx.doi.org/10.1016/j.bmc.2004.10.020] [PMID: 15598565]
[17]
Lu, L-Q.; Chen, J-R.; Xiao, W-J. Development of cascade reactions for the concise construction of diverse heterocyclic architectures. Acc. Chem. Res., 2012, 45(8), 1278-1293.
[http://dx.doi.org/10.1021/ar200338s] [PMID: 22577988]
[18]
Zhao, X.X.; Peng, C.; Zhang, H.; Qin, L.P. Sinomenium acutum: a review of chemistry, pharmacology, pharmacokinetics, and clinical use. Pharm. Biol., 2012, 50(8), 1053-1061.
[http://dx.doi.org/10.3109/13880209.2012.656847] [PMID: 22775422]
[19]
Abdelhadi, H.A.; Elwan, N.M.; Abdallah, T.A.; Pyrrolo, H.M.H. [2,1-a]isoquinolin-3-one derivatives obtained on reinvestigation of the reaction between C-ethoxy-carbonyl-N-arylformohydrazonoyl chlorides with 3,4-dihydro-6,7-dimthoxyisoquinoline-1-acetonitrile. J. Chem. Res., 1996, 262-293.
[20]
Elwan, N.M.; Abdelhadi, H.A.; Abdallah, T.A.; Hassaneen, H.M. Synthesis of [1, 2, 4] Triazolo [3, 4-a] Isoquinolines and Pyrrolo [2, 1-a] Isoquinolines using α-keto hydrazonoyl halides. Tetrahedron, 1996, 52(10), 3451-3456.
[http://dx.doi.org/10.1016/0040-4020(96)00024-5]
[21]
Awad, E.M.; Elwan, N.M.; Hassaneen, H.M.; Linden, A.; Heimgartner, H. Synthesis and Reactivity of 2-(6,7-Diethoxy-3,4-Dihydroisoquinolin- 1-Yl)acetonitrile towards Hydrazonoyl Halides. Helv. Chim. Acta, 2001, 84(5), 1172-1180.
[http://dx.doi.org/10.1002/1522-2675(20010516)84:5<1172::AID-HLCA1172>3.0.CO;2-X]
[22]
Abdallah, T.A.; Abdelhadi, H.A.; Hassaneen, H.M. Reactivity of 1-Methylisoquinoline. Synthesis of 2-(1-Isoquinolinemethylidene)-1,3,4-Thiadiazole Derivatives. Phosphorus Sulfur Silicon Relat. Elem., 2002, 177(1), 59-66.
[http://dx.doi.org/10.1080/10426500210218]
[23]
Abdallah, T.A.; Abdelhadi, H.A.; Ibrahim, A.A.; Hassaneen, H.M. Reactivity of 1-Methylisoquinoline. One Pot Synthesis of Benzo [a]-Quinolizine Derivatives. Synth. Commun., 2002, 32(4), 581-589.
[http://dx.doi.org/10.1081/SCC-120002405]
[24]
Huwaida, M.E. Hassaneen, Enas M. Awad, H. M. H. Studies with 6,7-Dimethoxy-3,4-Dihydroisoquinolin-1-Yl-Aceto-Nitrile: Novel Syntheses of 1-Azolyl- and Pyridoisoquinolines. Z. Naturfosch., 2007, 62b, 111-116.
[25]
Hassaneen, H.M.; Abdallah, T.A.; Awad, E.M. A Facile access for synthesis of novel isoquinoline-based heterocycles. Heterocycles, 2009, 78(6), 1507-1522.
[http://dx.doi.org/10.3987/COM-09-11648]
[26]
Hassaneen, H.M.; Hassaneen, H.M.; Mohammed, Y.S.; Pagni, R.M. Synthesis, Reactions and Antibacterial Activity of 3-Acetyl [1, 2, 4] Triazolo [3, 4-a] Isoquinoline Derivatives Using Chitosan as Heterogeneous Catalyst under Microwave Irradiation. Z. Naturforsch., 2011, 66b(3), 299-310.
[http://dx.doi.org/10.1515/znb-2011-0313]
[27]
Hassaneen, H.M.; Wardkhan, W.W.; Mohammed, Y.S. Synthesis and reactivity of 2-chloro-3-formylpyrido [2, 1-A] isoquinoline derivative: A novel routes to pyrazolo [3′, 4′: 4, 5] pyrido [2, 1-A] isoquinoline and isoquinolino [2, 1-G][1, 6] naphthyridines. Heterocycles, 2012, 85(12), 2933-2947.
[http://dx.doi.org/10.3987/COM-12-12572]
[28]
Hamdi, M. Hassaneen, W.W.W. and Y.S.M. A Novel Route to Isoquinoline[2,1-g][1,6]naphthyridine, Pyrazolo[5,1-A]isoquinoline and Pyridazino[4′,5′:3,4]pyrazolo[5,1-A]isoquinoline Derivatives With Evaluation of Antitumor Activities. Z. Naturforsch., 2013, 68b, 895-904.
[29]
Hamdi, M. Hassaneen, W.W.W. and Y.S.M. Synthesis and reactions of pyrido[2,1-a]isoquinolin-4-Yl formimidate derivatives and antimicrobial activities of isolated products. J. Heterocycl. Chem., 2017, 54, 2850-2858.
[http://dx.doi.org/10.1002/jhet.2891]
[30]
Hassaneen, H.M.; Huwaida, M.E. Hassaneen, and Y. S. M. Reactivity of 1-Methylisoquinoline Synthesis of Pyrazolyl Triazoloisoquinoline and Thia-Diazolyl Isoquinoline Derivatives. Nat. Sci., 2011, 3(8), 651-660.
[31]
Li, Y.; Zhao, Y.; Luo, M.; Tang, Z.; Cao, C.; Deng, K.; Yubo, L.; Yunhui, Z.; Mingjian, L.; Zilong, T. Synthesis of Isoquinolines Derivatives from O-Alkynyl Aldehydes. Youji Huaxue, 2016, 36(10), 2504.
[http://dx.doi.org/10.6023/cjoc201604031]
[32]
Zhao, Y-H.; Luo, Y.; Zhu, Y.; Wang, H.; Zhou, H.; Tan, H.; Zhou, Z.; Ma, Y-C.; Xie, W.; Tang, Z. Synthesis of Potential Anticancer 1-(1H-Indol-3-Yl)isoquinolines by Silver Nitrate Mediated Tandem Reactions of 2-Alkynylbenzaldehyde Azines and Indoles. Synlett, 2018, 29(6), 773-778.
[http://dx.doi.org/10.1055/s-0036-1591743]
[33]
Zhao, Y-H.; Li, Y.; Guo, T.; Tang, Z.; Deng, K.; Zhao, G. CuI-Catalyzed Domino Reactions for the Synthesis of Benzoxazine-Fused Isoquinolines under Microwave Irradiation. Synth. Commun., 2016, 46(4), 355-360.
[http://dx.doi.org/10.1080/00397911.2015.1137944]
[34]
Qiu, G.; Wu, J. Generation of N-Heterocycles via Tandem Reactions of N '-(2-Alkynylbenzylidene)hydrazides. Chem. Rec., 2016, 16(1), 19-34.
[http://dx.doi.org/10.1002/tcr.201500219] [PMID: 26493018]
[35]
Zhao, Y-H.; Li, Y.; Guo, T.; Tang, Z.; Xie, W.; Zhao, G. Selective Synthesis of pyrazolo[5,1-A]isoquinolines via 1,3-Dipolar Cycloaddition Reaction. Tetrahedron Lett., 2016, 57(21), 2257-2261.
[http://dx.doi.org/10.1016/j.tetlet.2016.04.037]
[36]
Osbond, J.M. 766. Chemical constitution and amoebicidal action. Part I. Synthesis of α-tetrahydro iso quinolino-ω-tetrahydro-1-iso quinolylalkanes related to emetine. J. Chem. Soc., 1951, 3464-3475.
[http://dx.doi.org/10.1039/JR9510003464]
[37]
Joshi, H.; Kamounah, F.S.; Gooijer, C.; van der Zwan, G.; Antonov, L. Excited state intramolecular proton transfer in some tautomeric azo dyes and schiff bases containing an intramolecular hydrogen bond. J. Photochem. Photobiol. Chem., 2002, 152(1–3), 183-191.
[http://dx.doi.org/10.1016/S1010-6030(02)00155-7]
[38]
Antonov, L.; Stoyanov, S. Azo-Quinonehydrazone Tautomerism in 2-Phenylazo-1-Naphthol. Dyes Pigments, 1995, 28(1), 31-39.
[http://dx.doi.org/10.1016/0143-7208(94)00076-E]
[39]
Stamos, J.; Sliwkowski, M.X.; Eigenbrot, C. Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor. J. Biol. Chem., 2002, 277(48), 46265-46272.
[http://dx.doi.org/10.1074/jbc.M207135200] [PMID: 12196540]
[40]
Cui, J.J.; Tran-Dubé, M.; Shen, H.; Nambu, M.; Kung, P-P.; Pairish, M.; Jia, L.; Meng, J.; Funk, L.; Botrous, I.; McTigue, M.; Grodsky, N.; Ryan, K.; Padrique, E.; Alton, G.; Timofeevski, S.; Yamazaki, S.; Li, Q.; Zou, H.; Christensen, J.; Mroczkowski, B.; Bender, S.; Kania, R.S.; Edwards, M.P. Structure based drug design of crizotinib (PF-02341066), a potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK). J. Med. Chem., 2011, 54(18), 6342-6363.
[http://dx.doi.org/10.1021/jm2007613] [PMID: 21812414]
[41]
Richardson, C.M.; Williamson, D.S.; Parratt, M.J.; Borgognoni, J.; Cansfield, A.D.; Dokurno, P.; Francis, G.L.; Howes, R.; Moore, J.D.; Murray, J.B.; Robertson, A.; Surgenor, A.E.; Torrance, C.J. Triazolo[1,5-a]pyrimidines as novel CDK2 inhibitors: protein structure-guided design and SAR. Bioorg. Med. Chem. Lett., 2006, 16(5), 1353-1357.
[http://dx.doi.org/10.1016/j.bmcl.2005.11.048] [PMID: 16325401]
[42]
Cossu, F.; Mastrangelo, E.; Milani, M.; Sorrentino, G.; Lecis, D.; Delia, D.; Manzoni, L.; Seneci, P.; Scolastico, C.; Bolognesi, M. Designing Smac-mimetics as antagonists of XIAP, cIAP1, and cIAP2. Biochem. Biophys. Res. Commun., 2009, 378(2), 162-167.
[http://dx.doi.org/10.1016/j.bbrc.2008.10.139] [PMID: 18992220]
[43]
Salama, S.K.; Mohamed, M.F.; Darweesh, A.F.; Elwahy, A.H.; Abdelhamid, I.A. Molecular docking simulation and anticancer assessment on human breast carcinoma cell line using novel bis(1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile) and bis(1,4-dihydropyrazolo[4′,3′:5,6]pyrano[2,3-b]pyridine-6-carbonitrile) derivatives. Bioorg. Chem., 2017, 71, 19-29.
[http://dx.doi.org/10.1016/j.bioorg.2017.01.009] [PMID: 28143658]
[44]
Ali, A.G.; Mohamed, M.F.; Abdelhamid, A.O.; Mohamed, M.S. A novel adamantane thiadiazole derivative induces mitochondria-mediated apoptosis in lung carcinoma cell line. Bioorg. Med. Chem., 2017, 25(1), 241-253.
[http://dx.doi.org/10.1016/j.bmc.2016.10.040] [PMID: 27847140]

Rights & Permissions Print Cite
Article Metrics
21
World Chagas Disease
© 2024 Bentham Science Publishers | Privacy Policy