Generic placeholder image

Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

Research Article

Synthesis of New Hydrazone Derivatives and Evaluation of their Efficacy as Proliferation Inhibitors in Human Cancer Cells

Author(s): Piotr Świątek*, Jolanta Saczko, Nina Rembiałkowska and Julita Kulbacka

Volume 15, Issue 8, 2019

Page: [903 - 910] Pages: 8

DOI: 10.2174/1573406415666190128100524

Price: $65

Abstract

Background: Hydrazine-hydrazones represent a group of bioactive compounds that display antibacterial, anti-inflammatory, antiviral or anticancer activities.

Objective: In this study, we designed new derivative compounds from groups of hydrazones.

Methods: The group of new derivatives was evaluated by the viability assay in human cancer and normal cells.

Results: The dimethylpyridine hydrazones showed potent inhibition of cell proliferation of breast, colon cancer cells, human melanoma and glioblastoma. Compound 12 inhibited proliferation of cancer cells exhibiting a drug-resistant phenotype (MCF-7/DX and LoVoDX) at low millimolar concentrations. Whereas, antimelanoma activity was revealed by Compounds 2, 4, 7 and 12.

Conclusion: The present results highlighted newly synthetized hydrazine derivatives an excellent base for the design of new anticancer agents and resistance inhibitors.

Keywords: Hydrazones, cancer cells, proliferation inhibitor, anticancer, synthesis, MTT.

Graphical Abstract
[1]
Okon, I.S.; Zou, M-H. Mitochondrial ROS and cancer drug resistance: Implications for therapy. Pharmacol. Res., 2015, 100, 170-174.
[http://dx.doi.org/10.1016/j.phrs.2015.06.013] [PMID: 26276086]
[2]
Holohan, C.; Van Schaeybroeck, S.; Longley, D.B.; Johnston, P.G. Cancer drug resistance: an evolving paradigm. Nat. Rev. Cancer, 2013, 13(10), 714-726.
[http://dx.doi.org/10.1038/nrc3599] [PMID: 24060863]
[3]
Kumar, D.; Maruthi Kumar, N.; Ghosh, S.; Shah, K. Novel bis(indolyl)hydrazide-hydrazones as potent cytotoxic agents. Bioorg. Med. Chem. Lett., 2012, 22(1), 212-215.
[http://dx.doi.org/10.1016/j.bmcl.2011.11.031] [PMID: 22123320]
[4]
Vicini, P.; Incerti, M.; Doytchinova, I.A.; La Colla, P.; Busonera, B.; Loddo, R. Synthesis and antiproliferative activity of benzo[d]isothiazole hydrazones. Eur. J. Med. Chem., 2006, 41(5), 624-632.
[http://dx.doi.org/10.1016/j.ejmech.2006.01.010] [PMID: 16540208]
[5]
Yu, X.; Shi, L.; Ke, S. Acylhydrazone derivatives as potential anticancer agents: Synthesis, bio-evaluation and mechanism of action. Bioorg. Med. Chem. Lett., 2015, 25(24), 5772-5776.
[http://dx.doi.org/10.1016/j.bmcl.2015.10.069] [PMID: 26546214]
[6]
Misra, S.; Ghatak, S.; Patil, N.; Dandawate, P.; Ambike, V.; Adsule, S.; Unni, D.; Venkateswara Swamy, K.; Padhye, S. Novel dual cyclooxygenase and lipoxygenase inhibitors targeting hyaluronan-CD44v6 pathway and inducing cytotoxicity in colon cancer cells. Bioorg. Med. Chem., 2013, 21(9), 2551-2559.
[http://dx.doi.org/10.1016/j.bmc.2013.02.033] [PMID: 23517721]
[7]
Lukasik, P.M.; Elabar, S.; Lam, F.; Shao, H.; Liu, X.; Abbas, A.Y.; Wang, S. Synthesis and biological evaluation of imidazo[4,5-b]pyridine and 4-heteroaryl-pyrimidine derivatives as anti-cancer agents. Eur. J. Med. Chem., 2012, 57, 311-322.
[http://dx.doi.org/10.1016/j.ejmech.2012.09.034] [PMID: 23085105]
[8]
Ahn, C.M.; Shin, W.S.; Bum Woo, H.; Lee, S.; Lee, H.W. Synthesis of symmetrical bis-alkynyl or alkyl pyridine and thiophene derivatives and their antiangiogenic activities. Bioorg. Med. Chem. Lett., 2004, 14(15), 3893-3896.
[http://dx.doi.org/10.1016/j.bmcl.2004.05.065] [PMID: 15225692]
[9]
Ari, F.; Aztopal, N.; Icsel, C.; Yilmaz, V.T.; Guney, E.; Buyukgungor, O.; Ulukaya, E. Synthesis, structural characterization and cell death-inducing effect of novel palladium(II) and platinum(II) saccharinate complexes with 2-(hydroxymethyl)pyridine and 2-(2-hydroxyethyl)pyridine on cancer cells in vitro. Bioorg. Med. Chem., 2013, 21(21), 6427-6434.
[http://dx.doi.org/10.1016/j.bmc.2013.08.050] [PMID: 24054490]
[10]
Zhang, Y.B.; Liu, W.; Yang, Y.S.; Wang, X.L.; Zhu, H.L.; Bai, L.F.; Qiu, X.Y. Synthesis, molecular modeling, and biological evaluation of 1,2,4-triazole derivatives containing pyridine as potential anti-tumor agents. Med. Chem. Res., 2013, 22, 3193-3203.
[http://dx.doi.org/10.1007/s00044-012-0306-5]
[11]
Karki, R.; Park, C.; Jun, K.Y.; Jee, J.G.; Lee, J.H.; Thapa, P.; Kadayat, T.M.; Kwon, Y.; Lee, E.S. Synthesis, antitumor activity, and structure-activity relationship study of trihydroxylated 2,4,6-triphenyl pyridines as potent and selective topoisomerase II inhibitors. Eur. J. Med. Chem., 2014, 84, 555-565.
[http://dx.doi.org/10.1016/j.ejmech.2014.07.058] [PMID: 25062006]
[12]
Varela, J.A.; Saá, C. Construction of pyridine rings by metal-mediated [2 + 2 + 2] cycloaddition. Chem. Rev., 2003, 103(9), 3787-3801.
[http://dx.doi.org/10.1021/cr030677f] [PMID: 12964884]
[13]
Świątek, P.; Strzelecka, M.; Urniaż, R.; Gębczak, K.; Gębarowski, T.; Gąsiorowski, K.; Malinka, W. Synthesis, COX-1/2 inhibition activities and molecular docking study of isothiazolopyridine derivatives. Bioorg. Med. Chem., 2017, 25(1), 316-326.
[http://dx.doi.org/10.1016/j.bmc.2016.10.036] [PMID: 27842798]
[14]
Saczko, J.; Dominiak, M.; Kulbacka, J.; Chwiłkowska, A.; Krawczykowska, H. A simple and established method of tissue culture of human gingival fibroblasts for gingival augmentation. Folia Histochem. Cytobiol., 2008, 46(1), 117-119.
[http://dx.doi.org/10.2478/v10042-008-0017-4] [PMID: 18296274]
[15]
Drąg-Zalesińska, M.; Drąg, M.; Poręba, M.; Borska, S.; Kulbacka, J.; Saczko, J. Anticancer properties of ester derivatives of betulin in human metastatic melanoma cells (Me-45). Cancer Cell Int., 2017, 17, 4.
[http://dx.doi.org/10.1186/s12935-016-0369-3] [PMID: 28053599]
[16]
Zawisza, T.; Malinka, W. Synthesis and properties of some derivatives of 2H-4,6-dimethylpyridoisothiazolin-3-one. Farmaco, 1985, 40, 124-132.
[17]
Palla, G.; Predieri, G.; Domiano, P.; Vignali, C.; Turner, W. Conformational behaviour and E/Z isomerization of N-acyl and N-aroylhydrazones. Tetrahedron, 1986, 42, 3649-3654.
[http://dx.doi.org/10.1016/S0040-4020(01)87332-4]
[18]
Wyrzykiewicz, E.; Prukała, D. New isomeric N-substituted hydrazones of 2-, 3-and 4-pyridinecarboxaldehydes. J. Chem., 1998, 35, 381-387.
[19]
Galić, N.; Perić, B.; Kojić-Prodić, B.; Cimerman, Z. Structural and spectroscopic characteristics of aroylhydrazones derived from nicotinic acid hydrazide. J. Mol. Struct., 2001, 551, 187-194.
[http://dx.doi.org/10.1016/S0022-2860(00)00703-1]
[20]
Pape, V.F.; Tóth, S.; Füredi, A.; Szebényi, K.; Lovrics, A.; Szabó, P.; Wiese, M.; Szakács, G. Design, synthesis and biological evaluation of thiosemicarbazones, hydrazinobenzothiazoles and arylhydrazones as anticancer agents with a potential to overcome multidrug resistance. Eur. J. Med. Chem., 2016, 117, 335-354.
[http://dx.doi.org/10.1016/j.ejmech.2016.03.078] [PMID: 27161177]
[21]
Nasr, T.; Bondock, S.; Youns, M. Anticancer activity of new coumarin substituted hydrazide-hydrazone derivatives. Eur. J. Med. Chem., 2014, 76, 539-548.
[http://dx.doi.org/10.1016/j.ejmech.2014.02.026] [PMID: 24607878]
[22]
Li, F.; Long, L.; Xiao, J.; Wang, C.; Li, W.; Li, S.; Zhao, C.; Wang, L. A novel hydroxyphenyl hydrazone derivate YCL0426 inhibits cancer cell proliferation through sequestering iron. Anticancer Drugs, 2017, 28(10), 1131-1140.
[http://dx.doi.org/10.1097/CAD.0000000000000557] [PMID: 28926421]
[23]
Tantak, M.P.; Klingler, L.; Arun, V.; Kumar, A.; Sadana, R.; Kumar, D. Design and synthesis of bis(indolyl)ketohydrazide-hydrazones: Identification of potent and selective novel tubulin inhibitors. Eur. J. Med. Chem., 2017, 136, 184-194.
[http://dx.doi.org/10.1016/j.ejmech.2017.04.078] [PMID: 28494255]
[24]
Hristova-Avakumova, N.; Yoncheva, K.; Nikolova-Mladenova, B.; Traykov, T.; Momekov, G.; Hadjimitova, V. 3-methoxy aroylhy-drazones - free radicals scavenging, anticancer and cytoprotective potency. Redox Rep., 2017, 22(6), 408-417.
[http://dx.doi.org/10.1080/13510002.2016.1276256] [PMID: 28073324]
[25]
Júnior, W.B.; Alexandre-Moreira, M.S.; Alves, M.A.; Perez-Rebolledo, A.; Parrilha, G.L.; Castellano, E.E.; Piro, O.E.; Barreiro, E.J.; Lima, L.M.; Beraldo, H. Analgesic and anti-inflammatory activities of salicylaldehyde 2-chlorobenzoyl hydrazone (H(2)LASSBio-466), salicylaldehyde 4-chlorobenzoyl hydrazone (H(2)LASSBio-1064) and their zinc(II) complexes. Molecules, 2011, 16(8), 6902-6915.
[http://dx.doi.org/10.3390/molecules16086902] [PMID: 21844840]
[26]
Jois, H.S.; Kalluraya, B.; Vishwanath, T. Synthesis, spectroscopic properties and antioxidant activity of bis-hydrazones and Schiff’s bases derived from terephthalic dihydrazide. J. Fluoresc., 2015, 25(3), 481-488.
[http://dx.doi.org/10.1007/s10895-015-1558-5] [PMID: 25820870]

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