Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

General Research Article

Newly Synthesized Arylazo Derivatives Induce Apoptosis and G2/M Cell Cycle Arrest With Molecular Docking Validation in Human Cancer Cell Lines

Author(s): Yara N. Laboud, Nourhan Hassan, Hamdi M. Hassaneen*, Huwaida M. E. Hassaneen, Fatma M. Saleh and Mohamed A. Mohamed Teleb

Volume 23, Issue 10, 2023

Published on: 09 March, 2023

Page: [1192 - 1203] Pages: 12

DOI: 10.2174/1871520623666230206105317

Price: $65

Abstract

Objective: We reported herein the synthesis of novel arylazo derivatives 3a-e incorporating isoquinoline moiety.

Methods: A coupling reaction of 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)acetonitrile 1 with diazotized heterocyclic amines 2 in ethanol in the presence of sodium acetate to give arylazo derivatives 3a-e.

Results: Cytotoxic effect of five arylazo derivatives on breast carcinoma MCF7 and hepatocellular carcinoma HepG2 was carried out, followed by molecular and functional-based assays, to estimate the anticancer effect of these compounds. The fibroblast growth factor receptor (FGFR) and epithelial growth factor receptor (EGFR) were found to interact and bind with the compounds 3a and 3d through several hydrophobic and hydrogen bonds, which were validated by molecular docking.

Conclusion: The two promising compounds 3a and 3d demonstrated various anticancer potential activities on tumorigenesis, cytotoxicity, and apoptotic effects, exhibited in the deregulation of the expression of different genes involved in apoptotic and anti-apoptotic mechanisms, cell cycle arrest at G2/M, and induction of apoptosis in both cell lines.

Graphical Abstract

[1]
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]
[2]
Edrees, M.M.; Farghaly, T.A.; El-Hag, F.A.A.; Abdalla, M.M. Antimicrobial, antitumor and 5α-reductase inhibitor activities of some hydrazonoyl substituted pyrimidinones. Eur. J. Med. Chem., 2010, 45(12), 5702-5707.
[http://dx.doi.org/10.1016/j.ejmech.2010.09.026] [PMID: 20933305]
[3]
Farghaly, T.A.; Abdalla, M.M. Synthesis, tautomerism, and antimicrobial, anti-HCV, anti-SSPE, antioxidant, and antitumor activities of arylazobenzosuberones. Bioorg. Med. Chem., 2009, 17(23), 8012-8019.
[http://dx.doi.org/10.1016/j.bmc.2009.10.012] [PMID: 19864149]
[4]
Ušćumlić, G.S.; Mijin, D.Z.; Valentić, N.V.; Vajs, V.V.; Sušić, B.M. Substituent and solvent effects on the UV/Vis absorption spectra of 5-(4-substituted arylazo)-6-hydroxy-4-methyl-3-cyano-2-pyridones. Chem. Phys. Lett., 2004, 397(1-3), 148-153.
[http://dx.doi.org/10.1016/j.cplett.2004.07.057]
[5]
Farghaly, T.A.; Abdallah, Z.A. Synthesis, azo-hydrazone tautomerism and antitumor screening of N-(3-ethoxycarbonyl-4,5,6,7-tetrahydro-benzo[b]thien-2-yl)-2-arylhydrazono-3-oxobutanamide derivatives. ARKIVOC, 2009, 2008(17), 295-305.
[http://dx.doi.org/10.3998/ark.5550190.0009.h28]
[6]
Garg, H.G.; Prakash, C. Potential antidiabetics. 11. Preparation of 4-arylazo-3,5-disubstituted-(2H)-1,2,6-thiadiazine 1,1-dioxides. J. Med. Chem., 1972, 15(4), 435-436.
[http://dx.doi.org/10.1021/jm00274a035] [PMID: 5019571]
[7]
Khalid, A.; Arshad, M.; Crowley, D.E. Accelerated decolorization of structurally different azo dyes by newly isolated bacterial strains. Appl. Microbiol. Biotechnol., 2008, 78(2), 361-369.
[http://dx.doi.org/10.1007/s00253-007-1302-4] [PMID: 18084755]
[8]
Park, C.; Lim, J.S.; Lee, Y.; Lee, B.; Kim, S.W.; Lee, J.; Kim, S. Optimization and morphology for decolorization of reactive black 5 by Funalia trogii. Enzyme Microb. Technol., 2007, 40(7), 1758-1764.
[http://dx.doi.org/10.1016/j.enzmictec.2006.12.005]
[9]
Raman, N.; Mitu, L.; Sakthivel, A. Pandi. MSS Studies on DNA cleavage and antimicrobial screening of transition metal complexes of 4-aminoantipyrine derivatives of N2O2 type. J. Iran Chem. Soc., 2009, 6(3), 738-748.
[http://dx.doi.org/10.1007/BF03246164]
[10]
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]
[11]
Hassaneen, H.M.; Hassaneen, H.M.E.; 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. J. Chem. Sci., 2011, 66, 299-310.
[http://dx.doi.org/10.1515/znb-2011-0313]
[12]
Banerjee, B. Role of the heterocycles to design anti-cancer agents. Anticancer. Agents Med. Chem., 2022, 22(19), 3194-3195.
[http://dx.doi.org/10.2174/187152062219220930154651] [PMID: 36221179]
[13]
Singh, R.; Tyagi, Y.K. jali, G. Synthesis and anti-cancer applications of benzimidazole derivatives-recent studies. Anticancer. Agents Med. Chem., 2022, 22(19), 3280-3290.
[http://dx.doi.org/10.2174/1871520622666220429134818] [PMID: 36221180]
[14]
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]
[15]
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]
[16]
Hassaneen, H.M.E.; Awad, E.M.; Hassaneen, H.M. Studies with 6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl-acetonitrile: Novel syntheses of 1-azolyl- And pyridoisoquinolines. Zeitschrift fur Naturforsch - Sect B. J. Chem. Sci., 2007, 62, 111-116.
[http://dx.doi.org/10.1515/znb-2007-0116]
[17]
Hassaneen, H.M.; Abdallah, T.A.; Awad, E.M. A facile access for synthesis of novel isoquinoline-based heterocycles. Heterocycles, 2009, 78, 1507-1522.
[http://dx.doi.org/10.3987/COM-09-11648]
[18]
Abdelhadi, H.A.; Elwan, N.M.; Abdallah, T.A.; Hassaneen, H.M. Pyrrolo[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.
[19]
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, 2933-2947.
[http://dx.doi.org/10.3987/COM-12-12572]
[20]
Hassaneen, H.M.; Wardkhan, W.W.; Mohammed, Y.S. 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. Zeitschrift fur Naturforsch. - Sect. B. J. Chem. Sci., 2013, 68, 895-904.
[http://dx.doi.org/10.5560/znb.2013-3101]
[21]
Hassaneen, H.M.; Wardakhan, W.W.; Mohammed, Y.S. Synthesis and reactions of pyrido[2,1-a]isoquinolin-4-yl formimidate derivatives and antimicrobial activities of isolated products. J. Heterocycl. Chem., 2017, 54(5), 2850-2858.
[http://dx.doi.org/10.1002/jhet.2891]
[22]
Hassaneen, H.M.; Hassaneen, H.M.E.; Mohammed, Y.S. Reactivity of 1-methylisoquinoline synthesis of pyrazolyl triazoloisoquinoline and thia-diazolyl isoquinoline derivatives. Nat. Sci., 2011, 3(8), 651-660.
[http://dx.doi.org/10.4236/ns.2011.38089]
[23]
Mohamed, M.F.; Sroor, F.M.; Ibrahim, N.S.; Salem, G.S.; El-Sayed, H.H.; Mahmoud, M.M.; Wagdy, M.A.M.; Ahmed, A.M.; Mahmoud, A.A.T.; Ibrahim, S.S.; Ismail, M.M.; Eldin, S.M.; Saleh, F.M.; Hassaneen, H.M.; Abdelhamid, I.A. Novel [l,2,4]triazolo[3,4-a]isoquinoline chalcones as new chemotherapeutic agents: Block IAP tyrosine kinase domain and induce both intrinsic and extrinsic pathways of apoptosis. Invest. New Drugs, 2021, 39(1), 98-110.
[http://dx.doi.org/10.1007/s10637-020-00987-2] [PMID: 32856275]
[24]
Tantawy, M.A.; Sroor, F.M.; Mohamed, M.F.; El-Naggar, M.E.; Saleh, F.M.; Hassaneen, H.M.; Abdelhamid, I.A. Molecular docking study, cytotoxicity, cell cycle arrest and apoptotic induction of novel chalcones incorporating thiadiazolyl isoquinoline in cervical cancer. Anticancer. Agents Med. Chem., 2020, 20(1), 70-83.
[http://dx.doi.org/10.2174/1871520619666191024121116] [PMID: 31696811]
[25]
Saleh, F.M.; Hassaneen, H.M.; Mohamed, M.F.; Mohamed, Y.S. Synthesis, cytotoxicity and docking simulation of novel annulated dihydroisoquinoline heterocycles. Mini Rev. Med. Chem., 2020, 20(12), 1166-1178.
[http://dx.doi.org/10.2174/1389557520666200130104632] [PMID: 32000650]
[26]
Saleh, F.M.; Hassaneen, H.M.; Butenschön, H.; Dräger, G.; Abdelhamid, I.A. Hantzsch-like three-component synthesis of tetracyclic 10b-azachrysenes: Unambiguous structural elucidation using X-ray crystallography and 2D-HMBC spectroscopy. Tetrahedron Lett., 2019, 60(46)151265
[http://dx.doi.org/10.1016/j.tetlet.2019.151265]
[27]
Abdelhamid, I.A.; Saleh, F.M.; Hassaneen, H.M. Hantzsch-like three-component synthesis of 9,10-dihydro-3h-10a-azaphenanthrene-2,4-dicarbonitriles. Synlett, 2020, 31(11), 1126-1128.
[http://dx.doi.org/10.1055/s-0039-1690902]
[28]
Saleh, F.M.; Hassaneen, H.M.; Abdelmoniem, A.M.; Elwahy, A.H.M.; Abdelhamid, I.A. Synthesis of novel bis(Pyrido[2,1-a]isoquinolines) linked to aliphatic or aromatic core via ether linkage. J. Heterocycl. Chem., 2019, 56(7), 1914-1921.
[http://dx.doi.org/10.1002/jhet.3565]
[29]
Teleb, M.A.M.; Hassaneen, H.M.; Abdelhadi, H.A.; Laboud, Y.N.; Saleh, F.M. Synthesis, antimicrobial and antitumor study of new pyrido[2,1-a]isoquinolines acetonitrile via isoquinoline-1-acetonitrile. Heterocycles, 2021, 102, 1729-1742.
[http://dx.doi.org/10.3987/COM-21-14494]
[30]
Teleb, M.A.M.; Hassan, N.; Hassaneen, H.M.; Hassaneen, H.M.E.; Laboud, Y.N.; Saleh, F.M. Synthesis, cytotoxicity and docking simulation of bioactive [1,2,4]triazolo[3,4-a]dihydroisoquinoline chalcone derivatives. Heterocycles, 2022, 104, 339-351.
[http://dx.doi.org/10.3987/COM-21-14579]
[31]
Mohamed, M.F.; Samir, N.; Ali, A.; Ahmed, N.; Ali, Y.; Aref, S.; Hossam, O.; Mohamed, M.S.; Abdelmoniem, A.M.; Abdelhamid, I.A. Apoptotic induction mediated p53 mechanism and Caspase-3 activity by novel promising cyanoacrylamide derivatives in breast carcinoma. Bioorg. Chem., 2017, 73, 43-52.
[http://dx.doi.org/10.1016/j.bioorg.2017.05.012] [PMID: 28601699]
[32]
Salama, S.K.; Mohamed, M.F.; Darweesh, A.F.; Elwahy, A.H.M.; 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]
[33]
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, 532-541.
[http://dx.doi.org/10.1016/j.ejmech.2017.11.045] [PMID: 29207336]
[34]
Adasme, M.F.; Linnemann, K.L.; Bolz, S.N.; Kaiser, F.; Salentin, S.; Haupt, V.J.; Schroeder, M. PLIP 2021: Expanding the scope of the protein-ligand interaction profiler to DNA and RNA. Nucleic Acids Res., 2021, 49(W1), W530-W534.
[http://dx.doi.org/10.1093/nar/gkab294] [PMID: 33950214]
[35]
Lee, H.A.; Chu, K.B.; Moon, E.K.; Kim, S.S.; Quan, F.S. Sensitization to oxidative stress and G2/M cell cycle arrest by histone deacetylase inhibition in hepatocellular carcinoma cells. Free Radic. Biol. Med., 2020, 147, 129-138.
[http://dx.doi.org/10.1016/j.freeradbiomed.2019.12.021] [PMID: 31870798]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy