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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Research Article

Design and Synthesis of 4(1H)-quinolone Derivatives as Autophagy Inducing Agents by Targeting ATG5 Protein

Author(s): Yifan Jia, Difei Yu, Qiuhua Huang, Xiaodong Zhang, Liqin Qiu, Rihui Cao*, Runlei Du* and Wenbin Liu*

Volume 17, Issue 7, 2020

Page: [884 - 890] Pages: 7

DOI: 10.2174/1570180816666191122113045

Price: $65

Abstract

Background: Quinolines have been characterized as a class of potential antitumor agents, and a large number of natural and synthetic quinolines acting as antitumor agents were reported.

Methods: A series of 7-chloro-4(1H)-quinolone derivatives were synthesized. The antiproliferative effect of these compounds was evaluated by MTT assay against five human tumor cell lines. The mechanism of action of the selected compound 7h was also investigated.

Results and Discussion: Most of the compounds had more potent antiproliferative activities than the lead compound 7-chloro-4(1H)-quinolone 6b. Compound 7h was found to be the most potent antiproliferative agent against human tumor cell lines. Further investigation demonstrated that compound 7h triggered ATG5-dependent autophagy of colorectal cancer cells by promoting the functions of LC3 proteins.

Conclusion: These results were useful for designing and discovering more potent novel antitumor agents endowed with better pharmacological profiles.

Keywords: Synthesis, quinolone, antiproliferative, autophagy, mechanism of action, ATG5 protein.

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[1]
Morling, J.; Chapman, C.; Logan, R. Gut, 2018, 67, A196.
[2]
Pfeiffer, P.; Kohne, C.H.; Qvortrup, C. Expert Rev.Anticancer Ther., 2018.
[3]
Bedri, S.; Sultan, A.A.; Alkhalaf, M.; Al Moustafa, A.E.; Vranic, S. Hum. Vaccin. Immunother. 2018.
[4]
Oh, M.; McBride, A.; Yun, S.; Bhattacharjee, S.; Slack, M.; Martin, J.R.; Jeter, J.; Abraham, I. BRCA1 and BRCA2 Gene Mutations and Colorectal Cancer Risk: Systematic Review and Meta-analysis. J. Natl. Cancer Inst., 2018, 110(11), 1178-1189.
[http://dx.doi.org/10.1093/jnci/djy148] [PMID: 30380096]
[5]
Issaka, R.B.; Avila, P.; Whitaker, E.; Bent, S.; Somsouk, M. Population health interventions to improve colorectal cancer screening by fecal immunochemical tests: A systematic review. Prev. Med., 2019, 118, 113-121.
[http://dx.doi.org/10.1016/j.ypmed.2018.10.021] [PMID: 30367972]
[6]
Call, J.A.; Eckhardt, S.G.; Camidge, D.R. Targeted manipulation of apoptosis in cancer treatment. Lancet Oncol., 2008, 9(10), 1002-1011.
[http://dx.doi.org/10.1016/S1470-2045(08)70209-2] [PMID: 18760670]
[7]
Wang, S.; Zhang, Y.; Chen, M.; Wang, Y.; Feng, Y.; Xu, Z.; Zhang, D.; Sun, Y.; Fu, Z. Association of genetic variants in ATR-CHEK1 and ATM-CHEK2 pathway genes with risk of colorectal cancer in a Chinese population. Oncotarget, 2018, 9(42), 26616-26624.
[http://dx.doi.org/10.18632/oncotarget.24299] [PMID: 29928473]
[8]
Hardiman, K.M. Update On Sporadic Colorectal Cancer Genetics. Clin. Colon Rectal Surg., 2018, 31(3), 147-152.
[http://dx.doi.org/10.1055/s-0037-1602234] [PMID: 29720900]
[9]
Mun, J.G.; Kee, J.Y.; Han, Y.H.; Lee, S.; Park, S.H.; Jeon, H.D.; Hong, S.H. Galla Rhois water extract inhibits lung metastasis by inducing AMPK mediated apoptosis and suppressing metastatic properties of colorectal cancer cells. Oncol. Rep., 2019, 41(1), 202-212.
[PMID: 30365120]
[10]
Zhang, Z.; Zhong, X.; Xiao, Y.; Chen, C. MicroRNA-296 inhibits colorectal cancer cell growth and enhances apoptosis by targeting ARRB1-mediated AKT activation. Oncol. Rep., 2019, 41(1), 619-629.
[PMID: 30365090]
[11]
Ye, X.; Zhou, X.J.; Zhang, H.F. Exploring the Role of Autophagy-Related Gene 5 (ATG5) Yields Important Insights Into Autophagy in Autoimmune/Autoinflammatory Diseases. Front. Immunol., 2018, 9, 2334.
[PMID: 30386331]
[12]
Wang, F.M.; Hu, Z.; Liu, X.; Feng, J.Q.; Augsburger, R.A.; Gutmann, J.L.; Glickman, G.N. Resveratrol represses tumor necrosis factor α/c-Jun N-terminal kinase signaling via autophagy in human dental pulp stem cells. Arch. Oral Biol., 2019, 97, 116-121.
[http://dx.doi.org/10.1016/j.archoralbio.2018.10.020] [PMID: 30384152]
[13]
Shroff, A.; Reddy, K.V.R. Autophagy gene ATG5 knockdown upregulates apoptotic cell death during Candida albicans infection in human vaginal epithelial cells. Am. J. Reprod. Immunol., 2018, 80(6)e13056
[http://dx.doi.org/10.1111/aji.13056] [PMID: 30303264]
[14]
Salahuddin, S.; Mazumder, A.; Shaharyar, M. Synthesis, antibacterial and anticancer evaluation of 5-substituted (1,3,4-oxadiazol-2-yl)quinoline. Med. Chem. Res., 2015, 24, 2514.
[15]
Li, K.; Li, Y.; Zhou, D.; Fan, Y.; Guo, H.; Ma, T.; Wen, J.; Liu, D.; Zhao, L. Synthesis and biological evaluation of quinoline derivatives as potential anti-prostate cancer agents and Pim-1 kinase inhibitors. Bioorg. Med. Chem., 2016, 24(8), 1889-1897.
[http://dx.doi.org/10.1016/j.bmc.2016.03.016] [PMID: 26979485]
[16]
Wang, X.; Jiang, N.; Zhao, S.; Xi, S.; Wang, J.; Jing, T.; Zhang, W.; Guo, M.; Gong, P.; Zhai, X. Design, synthesis and biological evaluation of novel 4-(2-fluorophenoxy)quinoline derivatives as selective c-Met inhibitors. Bioorg. Med. Chem., 2017, 25(3), 886-896.
[http://dx.doi.org/10.1016/j.bmc.2016.12.002] [PMID: 28011202]
[17]
Srivastava, S.K.; Jha, A.; Agarwal, S.K.; Mukherjee, R.; Burman, A.C. Synthesis and structure-activity relationships of potent antitumor active quinoline and naphthyridine derivatives. Anticancer. Agents Med. Chem., 2007, 7(6), 685-709.
[http://dx.doi.org/10.2174/187152007784111313] [PMID: 18045063]
[18]
Sun, J.; Zhu, H.; Yang, Z.M.; Zhu, H.L. Synthesis, molecular modeling and biological evaluation of 2-aminomethyl-5-(quinolin-2-yl)-1,3,4-oxadiazole-2(3H)-thione quinolone derivatives as novel anticancer agent. Eur. J. Med. Chem., 2013, 60, 23-28.
[http://dx.doi.org/10.1016/j.ejmech.2012.11.039] [PMID: 23279864]
[19]
Kumar, A.R.; Lingaiah, B.P.V.; Rao, P.S.; Narsaiah, B.; Sriram, D.; Sowjanya, P. Indian Journal of Chemistry Section B-Organic Chemistry Including. Med. Chem., 2015, 54, 1495.
[20]
Abdellatif, K.R.A.; Abdelall, E.K.A.; Abdelgawad, M.A.; Amin, D.M.E.; Omar, H.A. Med. Chem. Res., 2017, 26, 929.
[http://dx.doi.org/10.1007/s00044-017-1798-9]
[21]
Khelifi, I.; Naret, T.; Renko, D.; Hamze, A.; Bernadat, G.; Bignon, J.; Lenoir, C.; Dubois, J.; Brion, J.D.; Provot, O.; Alami, M. Design, synthesis and anticancer properties of IsoCombretaQuinolines as potent tubulin assembly inhibitors. Eur. J. Med. Chem., 2017, 127, 1025-1034.
[http://dx.doi.org/10.1016/j.ejmech.2016.11.012] [PMID: 28166995]
[22]
Marciniec, K.; Pawelczak, B.; Latocha, M.; Skrzypek, L.; Maciazek-Jurczyk, M.; Boryczka, S. Molecules, 2017, 22.
[23]
Aldred, K.J.; McPherson, S.A.; Wang, P.; Kerns, R.J.; Graves, D.E.; Turnbough, C.L., Jr; Osheroff, N. Drug interactions with Bacillus anthracis topoisomerase IV: biochemical basis for quinolone action and resistance. Biochemistry, 2012, 51(1), 370-381.
[http://dx.doi.org/10.1021/bi2013905] [PMID: 22126453]
[24]
Abouzid, K.; Shouman, S. Design, synthesis and in vitro antitumor activity of 4-aminoquinoline and 4-aminoquinazoline derivatives targeting EGFR tyrosine kinase. Bioorg. Med. Chem., 2008, 16(16), 7543-7551.
[http://dx.doi.org/10.1016/j.bmc.2008.07.038] [PMID: 18678492]
[25]
Wang, L.; Hou, X.; Fu, H.; Pan, X.; Xu, W.; Tang, W.; Fang, H. Design, synthesis and preliminary bioactivity evaluations of substituted quinoline hydroxamic acid derivatives as novel histone deacetylase (HDAC) inhibitors. Bioorg. Med. Chem., 2015, 23(15), 4364-4374.
[http://dx.doi.org/10.1016/j.bmc.2015.06.024] [PMID: 26149591]
[26]
Chen, Q.; Geng, W. Zhongguo Xin Yao Zazhi, 2005, 14, 1231.
[27]
Zhang, Z.; Xiao, X.; Su, T.; Wu, J.; Ren, J.; Zhu, J.; Zhang, X.; Cao, R.; Du, R. Synthesis, structure-activity relationships and preliminary mechanism of action of novel water-soluble 4-quinolone-3-carboxamides as antiproliferative agents. Eur. J. Med. Chem., 2017, 140, 239-251.
[http://dx.doi.org/10.1016/j.ejmech.2017.09.017] [PMID: 28942112]
[28]
Price, C.C.; Roberts, R.M. The synthesis of 4-hydroxyquinolines; through ethoxymethylene malonic ester. J. Am. Chem. Soc., 1946, 68, 1204-1208.
[http://dx.doi.org/10.1021/ja01211a020] [PMID: 20990951]
[29]
Lopez, I. PO, L.; Tucci, P.; Alvarez-Valin, F.; AC, R.; Marin, M. Different mutation profiles associated to P53 accumulation in colorectal cancer. Gene, 2012, 499(1), 81-87.
[PMID: 22373952]
[30]
Nasierowska-Guttmejer, A.; Trzeciak, L.; Nowacki, M.P.; Ostrowski, J. p53 protein accumulation and p53 gene mutation in colorectal cancer. Pathol. Oncol. Res., 2000, 6(4), 275-279.
[http://dx.doi.org/10.1007/BF03187331] [PMID: 11173660]
[31]
Hammel, P.; Leroy-Viard, K.; Chaumette, M.T.; Villaudy, J.; Falzone, M.C.; Rouillard, D.; Hamelin, R.; Boissier, B.; Remvikos, Y. Correlations between p53-protein accumulation, serum antibodies and gene mutation in colorectal cancer. Int. J. Cancer, 1999, 81(5), 712-718.
[http://dx.doi.org/10.1002/(SICI)1097-0215(19990531)81:5<712:AID-IJC7>3.0.CO;2-0] [PMID: 10328221]
[32]
Webley, K.M.; Shorthouse, A.J.; Royds, J.A. Effect of mutation and conformation on the function of p53 in colorectal cancer. J. Pathol., 2000, 191(4), 361-367.
[http://dx.doi.org/10.1002/1096-9896(2000)9999:9999<:AID-PATH660> 3.0.CO;2-2] [PMID: 10918210]
[33]
Katsumata, K.; Sumi, T.; Tomioka, H.; Aoki, T.; Koyanagi, Y. Induction of apoptosis by p53, bax, bcl-2, and p21 expressed in colorectal cancer. Int. J. Clin. Oncol., 2003, 8(6), 352-356.
[http://dx.doi.org/10.1007/s10147-003-0352-6] [PMID: 14663636]
[34]
Ye, J.; Li, J.; Wang, X.; Li, L. Medicinal supplement genipin induces p53 and Bax-dependent apoptosis in colon cancer cells. Oncol. Lett., 2018, 16(3), 2957-2964.
[http://dx.doi.org/10.3892/ol.2018.9025] [PMID: 30127884]
[35]
Coll, J.L.; Negoescu, A.; Louis, N.; Sachs, L.; Tenaud, C.; Girardot, V.; Demeinex, B.; Brambilla, E.; Brambilla, C.; Favrot, M. Antitumor activity of bax and p53 naked gene transfer in lung cancer: in vitro and in vivo analysis. Hum. Gene Ther., 1998, 9(14), 2063-2074.
[http://dx.doi.org/10.1089/hum.1998.9.14-2063] [PMID: 9759933]
[36]
Haghighat, P.; Timiryasova, T.M.; Chen, B.; Kajioka, E.H.; Gridley, D.S.; Fodor, I. Antitumor effect of IL-2, p53, and bax gene transfer in C6 glioma cells. Anticancer Res., 2000, 20(3A), 1337-1342.
[PMID: 10928041]
[37]
Kagawa, S.; Gu, J.; Swisher, S.G.; Ji, L.; Roth, J.A.; Lai, D.; Stephens, L.C.; Fang, B. Antitumor effect of adenovirus-mediated Bax gene transfer on p53-sensitive and p53-resistant cancer lines. Cancer Res., 2000, 60(5), 1157-1161.
[PMID: 10728665]

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