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Current Topics in Medicinal Chemistry

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ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

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Research Article

Antiproliferative Activity of 8-methoxy Ciprofloxacin-Hydrozone/Acylhydrazone Scaffolds

Author(s): Li-Ping Wang, Zhi Xu*, Gui-Ying Deng* and Sha-Li Xu

Volume 20, Issue 21, 2020

Page: [1911 - 1915] Pages: 5

DOI: 10.2174/1568026620666200603105644

Price: $65

Abstract

Aims: A series of 8-methoxy ciprofloxacin- hydrazone/acylhydrazone hybrids were evaluated for their activity against a panel of cancer cell lines including HepG2 liver cancer cells, MCF-7, doxorubicin- resistant MCF-7 (MCF-7/DOX) breast cancer cells, DU-145 and multidrug-resistant DU145 (MDR DU-145) prostate cancer cells to seek for novel anticancer agents.

Background: Ciprofloxacin with excellent pharmacokinetic properties as well as few side effects, is one of the most common used antibacterial agents. Notably, Ciprofloxacin could induce cancer cells apoptosis, and cell cycle arrest at the S/G2 stage. The structure-activity relationship reveals that the introduction of the methoxy group into the C-8 position of the fluoroquinolone moiety has resulted in a greater binding affinity to the binding site, and 8-methoxy ciprofloxacin derivatives have proved a variety of biological activities even against drug-resistant organisms. However, to the best of our current knowledge, there are no studies that have reported the anticancer activity of 8-methoxy ciprofloxacin derivatives so far. Furthermore, many fluoroquinolone-hydrazone/acylhydrazone hybrids possess promising anticancer activity. Thus, it is rational to screen the anticancer activity of 8-methoxy ciprofloxacin derivatives.

Objective: To enrich the structure-activity relationship and provide new anticancer candidates for further investigations.

Methods: The desired 8-methoxy ciprofloxacin-hydrazone/acylhydrazone hybrids 5 and 6 were screened for their in vitro anticancer activity against liver cancer cells HepG2, breast cancer cells MCF-7, MCF7/DOX, prostate cancer cells DU-145 and MDR DU-145 by MTT assay.

Results: Some of 8-methoxy ciprofloxacin-hydrazone hybrids showed potential activity against HepG2, MCF-7, MCF-7/DOX, DU-145 and MDR DU-145 cancer cell lines, low cytotoxicity towards VERO cells and promising inhibitory activity on tubulin polymerization.

Conclusion: Compounds 5d and 5f showed promising anticancer activity, low cytotoxicity, and potential tubulin polymerization inhibitory activity, were worthy of investigation.

Other: The structure-activity relationship was enriched.

Keywords: Ciprofloxacin, Hydrazone, Acylhydrazone, Anticancer, Tubulin Polymerization, Structure-activity relationship.

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[1]
International Agency for Research on Cancer. Latest global cancer data: Cancer burden rises to 18.1 million new cases and 9.6 million cancer deaths in 2018. 2018.Available from: . https://www.iarc.fr/featurednews/latest-global-cancer-data-cancer-burden-rises-to-18-1-millionnew-cases-and-9-6-million-cancer-deaths-in-2018/
[2]
International Agency for Research on Cancer. Cancer Tomorrow. Available from:, , https://gco.iarc.fr/tomorrow/graphicisotype? type=0&population=900&mode=population&sex=0&cancer=39&age_group=value&apc_male=0&apc_female=0
[3]
Mu, L.M.; Ju, R.J.; Liu, R.; Bu, Y.Z.; Zhang, J.Y.; Li, X.Q.; Zeng, F.; Lu, W.L. Dual-functional drug liposomes in treatment of resistant cancers. Adv. Drug Deliv. Rev., 2017, 115, 46-56.
[http://dx.doi.org/10.1016/j.addr.2017.04.006] [PMID: 28433739]
[4]
Zhang, L.; Li, Y.; Chen, Q.; Xia, Y.; Zheng, W.; Jiang, X. The construction of drug-resistant cancer cell lines by CRISPR/Cas9 system for drug screening. Sci. Bull. (Beijing), 2018, 63(21), 1411-1419.
[http://dx.doi.org/10.1016/j.scib.2018.09.024]
[5]
Zhang, G.F.; Zhang, S.; Pan, B.; Liu, X.; Feng, L.S. 4-Quinolone derivatives and their activities against Gram positive pathogens. Eur. J. Med. Chem., 2018, 143, 710-723.
[http://dx.doi.org/10.1016/j.ejmech.2017.11.082] [PMID: 29220792]
[6]
Gao, F.; Wang, P.; Yang, H.; Miao, Q.; Ma, L.; Lu, G. Recent developments of quinolone-based derivatives and their activities against Escherichia coli. Eur. J. Med. Chem., 2018, 157, 1223-1248.
[http://dx.doi.org/10.1016/j.ejmech.2018.08.095] [PMID: 30193220]
[7]
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]
[8]
Suaifan, G.A.R.Y.; Mohammed, A.A.M. Fluoroquinolones structural and medicinal developments (2013-2018): Where are we now? Bioorg. Med. Chem., 2019, 27(14), 3005-3060.
[http://dx.doi.org/10.1016/j.bmc.2019.05.038] [PMID: 31182257]
[9]
Yadav, V.; Talwar, P. Repositioning of fluoroquinolones from antibiotic to anti-cancer agents: An underestimated truth. Biomed. Pharmacother., 2019, 111, 934-946.
[http://dx.doi.org/10.1016/j.biopha.2018.12.119] [PMID: 30841473]
[10]
Xu, Z.; Zhao, S.J.; Lv, Z.S.; Gao, F.; Wang, Y.; Zhang, F.; Bai, L.; Deng, J.L. Fluoroquinolone-isatin hybrids and their biological activities. Eur. J. Med. Chem., 2019, 162, 396-406.
[http://dx.doi.org/10.1016/j.ejmech.2018.11.032] [PMID: 30453247]
[11]
Zhang, G.F.; Liu, X.; Zhang, S.; Pan, B.; Liu, M.L. Ciprofloxacin derivatives and their antibacterial activities. Eur. J. Med. Chem., 2018, 146, 599-612.
[http://dx.doi.org/10.1016/j.ejmech.2018.01.078] [PMID: 29407984]
[12]
Hu, Y.Q.; Zhang, S.; Xu, Z.; Lv, Z.S.; Liu, M.L.; Feng, L.S. 4-Quinolone hybrids and their antibacterial activities. Eur. J. Med. Chem., 2017, 141, 335-345.
[http://dx.doi.org/10.1016/j.ejmech.2017.09.050] [PMID: 29031077]
[13]
Ahadi, H.; Emami, S. Modification of 7-piperazinylquinolone antibacterials to promising anticancer lead compounds: Synthesis and in vitro studies. Eur. J. Med. Chem., 2020, 187, 111970
[http://dx.doi.org/10.1016/j.ejmech.2019.111970] [PMID: 31881454]
[14]
Zhao, B.Y.; Pine, R.; Domagala, J.; Drlica, K. Fluoroquinolone action against clinical isolates of Mycobacterium tuberculosis: effects of a C-8 methoxyl group on survival in liquid media and in human macrophages. Antimicrob. Agents Chemother., 1999, 43(3), 661-666.
[http://dx.doi.org/10.1128/AAC.43.3.661] [PMID: 10049284]
[15]
Sanchez, J.P.; Gogliotti, R.D.; Domagala, J.M.; Gracheck, S.J.; Huband, M.D.; Sesnie, J.A.; Cohen, M.A.; Shapiro, M.A. The synthesis, structure-activity, and structure-side effect relationships of a series of 8-alkoxy- and 5-amino-8-alkoxyquinolone antibacterial agents. J. Med. Chem., 1995, 38(22), 4478-4487.
[http://dx.doi.org/10.1021/jm00022a013] [PMID: 7473575]
[16]
Feng, L.S.; Liu, M.L.; Zhang, S.; Chai, Y.; Wang, B.; Zhang, Y.B.; Lv, K.; Guan, Y.; Guo, H.Y.; Xiao, C.L. Synthesis and in vitro antimycobacterial activity of 8-OCH(3) ciprofloxacin methylene and ethylene isatin derivatives. Eur. J. Med. Chem., 2011, 46(1), 341-348.
[http://dx.doi.org/10.1016/j.ejmech.2010.11.023] [PMID: 21146257]
[17]
Gao, L.Z.; Xie, Y.S.; Li, T.; Huang, W.L.; Hu, G.Q. [Synthesis, antitumor activity and SAR of C-3 oxadiazole sulfanylacetylhydrazone-substituted fluoroquinolone analogues]. Yao Xue Xue Bao, 2014, 49(12), 1694-1698.
[PMID: 25920199]
[18]
Hu, G.Q.; Hou, L.L.; Wang, G.Q.; Duan, N.N.; Wen, X.Y.; Cao, T.Y. Synthesis and antitumor and antibacterial activities of fluoroquinolone C-3 isosteres I. Norfloxacin C-3 carbonylhydrazone derivatives. J. Chin. Pharmaceut. Univ., 2012, 43, 298-301.
[19]
Sun, J.P.; Shi, Z.Y.; Liu, S.M.; Kang, Y.H.; Hu, G.Q.; Huangfu, C.S.; Deng, J.B.; Liu, B. Trimethoxy-benzaldehyde levofloxacin hydrazone inducing the growth arrest and apoptosis of human hepatocarcinoma cells. Cancer Cell Int., 2013, 13(1), 67-76.
[http://dx.doi.org/10.1186/1475-2867-13-67] [PMID: 23819802]
[20]
Shi, Z.Y.; Li, Y.Q.; Kang, Y.H.; Hu, G.Q.; Huang-fu, C.S.; Deng, J.B.; Liu, B. Piperonal ciprofloxacin hydrazone induces growth arrest and apoptosis of human hepatocarcinoma SMMC-7721 cells. Acta Pharmacol. Sin., 2012, 33(2), 271-278.
[http://dx.doi.org/10.1038/aps.2011.158] [PMID: 22301863]
[21]
Xu, Q.J.; Hou, L.L.; Wu, X.K.; Xie, S.Q.; Hu, G.Q.; Huang, W.L. Synthesis and antitumor activity of ciprofloxacin bis-(C3/C7 hydrozone)s. J. Chin. Pharmaceut. Univer., 2013, 44, 35-38.
[22]
Xu, Z.; Zhang, S.; Feng, L.S.; Li, X.N.; Huang, G.C.; Chai, Y.; Lv, Z.S.; Guo, H.Y.; Liu, M.L. Synthesis and in vitro antimycobacterial and antibacterial activity of 8-OMe ciprofloxacin-hydrozone/azole hybrids. Molecules, 2017, 22(7), e1171
[http://dx.doi.org/10.3390/molecules22071171] [PMID: 28703766]

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