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Anti-Cancer Agents in Medicinal Chemistry

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

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Research Article

In Vitro Anticancer Evaluation of Some Synthesized 2H-Quinolinone and Halogenated 2H-Quinolinone Derivatives as Therapeutic Agents

Author(s): Rahma M. Abd El-Aziz*, Islam Zaki, Ibrahim M. El-Deen, Marwa S. Abd-Rahman and Faten Z. Mohammed

Volume 20, Issue 18, 2020

Page: [2304 - 2315] Pages: 12

DOI: 10.2174/1871520620666200811122753

Price: $65

Abstract

Background: Searching for new cytotoxic agents with apoptosis induction may represent a viable strategy for cancer treatment to overcome the increased resistance to available anticancer agents.

Objective: The purpose of the current study was aimed at preparation and anticancer evaluation of two new series of 2H-quinolinone and halogenated 2H-quinolinone derivatives against two cancer cell lines.

Methods: Two new series of 2H-quinolinone and halogenated 2H-quinolinone derivatives were prepared and screened for their cytotoxicity against breast MCF-7 and liver HepG-2 cancer cell lines as well as normal breast MCF-10a.

Results: The tested molecules revealed good cytotoxicity and selectivity toward cancer cell lines relative to normal cells. These compounds were analyzed by DNA flow cytometry on MCF-7 cells. They were found to cause G2/M phase arrest and induced apoptosis at the pre-G1 phase. In addition, increased caspase 3/7 activity and decreased osteopontin expression verified the apoptotic activity.

Conclusion: The potent compounds discovered in this study can be a hit for the discovery of new cytotoxic agents and are worthy of further investigation.

Keywords: Quinolinone, cell cycle analysis, annexin V-FITC/PI, caspase 3/7, osteopontin, topoisomerase, apoptosis.

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[1]
Gao, F.; Zhang, X.; Wang, T.; Xiao, J. Quinolone hybrids and their anti-cancer activities: An overview. Eur. J. Med. Chem., 2019, 165, 59-79.
[http://dx.doi.org/10.1016/j.ejmech.2019.01.017] [PMID: 30660827]
[2]
Jain, S.; Chandra, V.; Jain, P.K.; Pathak, K.; Pathak, D.; Vaidya, A. Comprehensive review on current developments of quinoline-based anticancer agents. Arab. J. Chem., 2019, 12, 4920-4946.
[http://dx.doi.org/10.1016/j.arabjc.2016.10.009]
[3]
Gasparotto, V.; Castagliuolo, I.; Chiarelotto, G.; Pezzi, V.; Montanaro, D.; Brun, P.; Palù, G.; Viola, G.; Ferlin, M.G. Synthesis and biological activity of 7-phenyl-6,9-dihydro-3H-pyrrolo[3,2-f]quinolin-9-ones: A new class of antimitotic agents devoid of aromatase activity. J. Med. Chem., 2006, 49(6), 1910-1915.
[http://dx.doi.org/10.1021/jm0510676] [PMID: 16539377]
[4]
Ryckebusch, A.; Garcin, D.; Lansiaux, A.; Goossens, J.F.; Baldeyrou, B.; Houssin, R.; Bailly, C.; Hénichart, J.P. Synthesis, cytotoxicity, DNA interaction, and topoisomerase II inhibition properties of novel indeno[2,1-c]quinolin-7-one and indeno[1,2-c]isoquinolin-5,11-dione derivatives. J. Med. Chem., 2008, 51(12), 3617-3629.
[http://dx.doi.org/10.1021/jm800017u] [PMID: 18507368]
[5]
Schmidt, F.; Knobbe, C.B.; Frank, B.; Wolburg, H.; Weller, M. The topoisomerase II inhibitor, genistein, induces G2/M arrest and apoptosis in human malignant glioma cell lines. Oncol. Rep., 2008, 19(4), 1061-1066.
[http://dx.doi.org/10.3892/or.19.4.1061] [PMID: 18357397]
[6]
Ahsan, M.J.; Yadav, R.; Jadav, S.S. Synthesis, anti-cancer and molecular docking studies of newer quinoline analogues. 1st International Electronic Congress on Medicinal Chemistry, 2015. Available at: https://sciforum.net/conference/ecmc-1
[http://dx.doi.org/10.3390/ecmc-1-A033]
[7]
Rizzk, Y.W.; El-Deen, I.M.; Mohammed, F.Z.; Abdelhamid, M.S.; Khedr, A.I.M. In vitro antitumor evaluation of some hybrid molecules containing coumarin and quinolinone moieties. Anticancer. Agents Med. Chem., 2019, 19(16), 2010-2018.
[http://dx.doi.org/10.2174/1871520619666190930143856] [PMID: 31566140]
[8]
Moustafa, A.M.Y.; Bakare, S.B. Synthesis of hybrid 7-hydroxy quinolinone derivatives as anti breast cancer drugs. Res. Chem. Intermed., 2019, 45, 3895-3912.
[http://dx.doi.org/10.1007/s11164-019-03827-y]
[9]
Vistica, D.T.; Skehan, P.; Scudiero, D.; Monks, A.; Pittman, A.; Boyd, M.R. Tetrazolium-based assays for cellular viability: A critical examination of selected parameters affecting formazan production. Cancer Res., 1991, 51(10), 2515-2520.
[PMID: 2021931]
[10]
Kassab, A.E.; Gedawy, E.M. Novel ciprofloxacin hybrids using Biology Oriented Drug Synthesis (BIODS) approach: Anticancer activity, effects on cell cycle profile, caspase-3 mediated apoptosis, topoisomerase II inhibition, and antibacterial activity. Eur. J. Med. Chem., 2018, 150, 403-418.
[http://dx.doi.org/10.1016/j.ejmech.2018.03.026] [PMID: 29547830]
[11]
Shi, J.B.; Chen, L.Z.; Wang, Y.; Xiou, C.; Tang, W.J.; Zhou, H.P.; Liu, X.H.; Yao, Q.Z. Benzophenone-nucleoside derivatives as telomerase inhibitors: Design, synthesis and anticancer evaluation in vitro and in vivo. Eur. J. Med. Chem., 2016, 124, 729-739.
[http://dx.doi.org/10.1016/j.ejmech.2016.09.011] [PMID: 27639364]
[12]
Wu, C.S.; Chen, Y-J.; Chen, J.J.; Shieh, J.J.; Huang, C-H.; Lin, P.S.; Chang, G.C.; Chang, J.T.; Lin, C.C. Terpinen-4-ol induces apoptosis in human nonsmall cell lung cancer in vitro and in vivo. Evid.-. Based Complem. Altern. Med., 2012, 13, 121-129.
[13]
Hafez, S.S.; El Sebai, A.A.; Abd, A.; Aziz, M.; Mahmoud, M.; El Maraghy, M.; Khalifa, M.; Musa, N. Alfa-fetoprotein L3 subfraction and osteopontin: Novel markers for the diagnosis of hepatocellular carcinoma. J. Am. Sci., 2013, 9, 322-328.
[14]
Opydo-Chanek, M.; Śladowska, K.; Blicharski, K.; Mikeš, J.; Fedoročko, P.; Niemeyer, U.; Mazur, L. Comparison of in vitro antileukemic activity of 4-hydroperoxyifosfamide and 4-hydroperoxycyclophosphamide. Anticancer Res., 2017, 37(11), 6355-6361.
[PMID: 29061820]
[15]
Bikadi, Z.; Hazai, E. Application of the PM6 semi-empirical method to modeling proteins enhances docking accuracy of AutoDock. J. Cheminform., 2009, 1, 15-27.
[http://dx.doi.org/10.1186/1758-2946-1-15] [PMID: 20150996]
[16]
Morris, G.M.; Goodsell, D.S.; Halliday, R.S.; Huey, R.; Hart, W.E.; Olson, A.J.; Belew, R.K. Automated docking using a Lamarckian genetic algorithm and empirical free energy binding function. J. Comput. Chem., 1998, 19, 1639-1662.
[http://dx.doi.org/10.1002/(SICI)1096-987X(19981115)19:14<1639:AID-JCC10>3.0.CO;2-B]
[17]
Solis, F.J.; Wets, R.J.B. Minimization by random search techniques. Math. Oper. Res., 1981, 6, 19-30.
[http://dx.doi.org/10.1287/moor.6.1.19]
[18]
Han, X.; Wang, W.; He, J.; Jiang, L.; Li, X. Osteopontin as a biomarker for osteosarcoma therapy and prognosis. Oncol. Lett., 2019, 17(3), 2592-2598.
[http://dx.doi.org/10.3892/ol.2019.9905] [PMID: 30854034]
[19]
Shim, M.K.; Yoon, H.Y.; Lee, S.; Jo, M.K.; Park, J.; Kim, J.H.; Jeong, S.Y.; Kwon, I.C.; Kim, K. Caspase-3/-7-specific metabolic precursor for bioorthogonal tracking of tumor apoptosis. Sci. Rep., 2017, 7(1), 16635-16644.
[http://dx.doi.org/10.1038/s41598-017-16653-2] [PMID: 29192289]
[20]
Beteringhe, A.; Racuciu, C.; Balan, C.; Patron, L.; Stoican, E. Molecular docking studies involving transition metal complexes (Zn (II), Co (II), Cu (II), Fe (II), Ni (II) with Cholic Acid (AC) as ligand against Aurora A kinase. Adv. Mat. Res., 2013, 787, 236-240.
[21]
Hosny, N.M.; Hussien, M.A.; Radwan, F.M.; Nawar, N. Synthesis, spectral characterization and DNA binding of Schiff-base metal complexes derived from 2-amino-3-hydroxyprobanoic acid and acetylacetone. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2014, 132, 121-129.
[http://dx.doi.org/10.1016/j.saa.2014.04.165] [PMID: 24858353]

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