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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

Anticancer Potential of a Synthetic Quinoline, 9IV-c, by Inducing Apoptosis in A549 Cell and In vivo BALB/c Mice Models

Author(s): Salimeh Mirzaei, Farhad Eisvand, Mojgan Nejabat, Razieh Ghodsi and Farzin Hadizadeh*

Volume 24, Issue 3, 2024

Published on: 24 November, 2023

Page: [185 - 192] Pages: 8

DOI: 10.2174/0118715206267446231103075806

Price: $65

Abstract

Background: In a previous work from the author of this study, the compound of 9IV-c, ((E)-2-(3,4- dimethoxystyryl)-6,7,8-trimethoxy-N-(3,4,5-trimethoxyphenyl)quinoline-4-amine) was synthesized, and the effects of potent activity on the multiple human tumor cell lines were evaluated considering the spindle formation together with the microtubule network.

Methods: Accordingly, cytotoxic activity, apoptotic effects, and the therapeutic efficiency of compound 9IV-c on A549 and C26 cell lines were investigated in this study.

Results: The compound 9IV-c demonstrated high cytotoxicity against A549 and C26 cell lines with IC50 = 1.66 and 1.21 μM, respectively. The flow cytometric analysis of the A549 cancer cell line treated with compound 9IVc showed that This compound induced cell cycle arrest at the G2/M phase and apoptosis. Western blotting analysis displayed that compound 9IV-c also elevated the Bax/Bcl-2 ratio and increased the activation of caspase-9 and -3 but not caspase-8.

Conclusion: These data presented that the intrinsic pathway was responsible for 9IV-c -induced cell apoptosis. In vivo studies demonstrated that treatment with the compound of 9IV-c at 10 mg/kg dose led to a decrease in tumor growth compared to the control group. It was found that there was not any apparent body weight loss in the period of treatment. Also, in the vital organs of the BALB/c mice, observable pathologic changes were not detected.

Keywords: Quinoline derivative, 9IV-c, Apoptosis, In vivo antitumor activity, A549 and C26 cell lines, Bax/Bcl-2 ratio.

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[1]
Giordano, S.; Petrelli, A. From single- to multi-target drugs in cancer therapy: When aspecificity becomes an advantage. Curr. Med. Chem., 2008, 15(5), 422-432.
[http://dx.doi.org/10.2174/092986708783503212] [PMID: 18288997]
[2]
Nepali, K.; Sharma, S.; Sharma, M.; Bedi, P.M.S.; Dhar, K.L. Rational approaches, design strategies, structure activity relationship and mechanistic insights for anticancer hybrids. Eur. J. Med. Chem., 2014, 77, 422-487.
[http://dx.doi.org/10.1016/j.ejmech.2014.03.018] [PMID: 24685980]
[3]
Al-Warhi, T.; Sabt, A.; Elkaeed, E.B.; Eldehna, W.M. Recent advancements of coumarin-based anticancer agents: An up-to-date review. Bioorg. Chem., 2020, 103, 104163.
[http://dx.doi.org/10.1016/j.bioorg.2020.104163] [PMID: 32890989]
[4]
Bukhari, S.N.A.; Kumar, G.B.; Revankar, H.M.; Qin, H.L. Development of combretastatins as potent tubulin polymerization inhibitors. Bioorg. Chem., 2017, 72, 130-147.
[http://dx.doi.org/10.1016/j.bioorg.2017.04.007] [PMID: 28460355]
[5]
Haider, K.; Rahaman, S.; Yar, M.S.; Kamal, A. Tubulin inhibitors as novel anticancer agents: An overview on patents (2013-2018). Expert Opin. Ther. Pat., 2019, 29(8), 623-641.
[http://dx.doi.org/10.1080/13543776.2019.1648433] [PMID: 31353978]
[6]
Mirzaei, S.; Eisvand, F.; Hadizadeh, F.; Mosaffa, F.; Ghodsi, R. Design, synthesis, and biological evaluation of novel 5,6,7-trimethoxy quinolines as potential anticancer agents and tubulin polymerization inhibitors. Iran. J. Basic Med. Sci., 2020, 23(12), 1527-1537.
[PMID: 33489025]
[7]
Mirzaei, S.; Qayumov, M.; Gangi, F.; Behravan, J.; Ghodsi, R. Synthesis and biological evaluation of oxazinonaphthalene-3-one derivatives as potential anticancer agents and tubulin inhibitors. Iran. J. Basic Med. Sci., 2020, 23(11), 1388-1395.
[PMID: 33235695]
[8]
Castedo, M.; Perfettini, J.L.; Roumier, T.; Andreau, K.; Medema, R.; Kroemer, G. Cell death by mitotic catastrophe: A molecular definition. Oncogene, 2004, 23(16), 2825-2837.
[http://dx.doi.org/10.1038/sj.onc.1207528] [PMID: 15077146]
[9]
Kamal, A.; Shaik, A.B.; Jain, N.; Kishor, C.; Nagabhushana, A.; Supriya, B.; Bharath, K.G.; Chourasiya, S.S.; Suresh, Y.; Mishra, R.K.; Addlagatta, A. Design and synthesis of pyrazole–oxindole conjugates targeting tubulin polymerization as new anticancer agents. Eur. J. Med. Chem., 2015, 92, 501-513.
[http://dx.doi.org/10.1016/j.ejmech.2013.10.077] [PMID: 25599948]
[10]
Mirzaei, S.; Eisvand, F.; Hadizadeh, F.; Mosaffa, F.; Ghasemi, A.; Ghodsi, R. Design, synthesis and biological evaluation of novel 5,6,7-trimethoxy-N-aryl-2-styrylquinolin-4-amines as potential anticancer agents and tubulin polymerization inhibitors. Bioorg. Chem., 2020, 98, 103711.
[http://dx.doi.org/10.1016/j.bioorg.2020.103711] [PMID: 32179282]
[11]
Molina, J.R.; Yang, P.; Cassivi, S.D.; Schild, S.E.; Adjei, A.A. Non-small cell lung cancer: Epidemiology, risk factors, treatment, and survivorship. Mayo clinic proceedings; Elsevier, 2008.
[12]
El-Shafey, H.W.; Gomaa, R.M.; El-Messery, S.M.; Goda, F.E. Synthetic approaches, anticancer potential, HSP90 inhibition, multitarget evaluation, molecular modeling and apoptosis mechanistic study of thioquinazolinone skeleton: Promising antibreast cancer agent. Bioorg. Chem., 2020, 101, 103987.
[http://dx.doi.org/10.1016/j.bioorg.2020.103987] [PMID: 32540783]
[13]
Shoemaker, R.H. The NCI60 human tumour cell line anticancer drug screen. Nat. Rev. Cancer, 2006, 6(10), 813-823.
[http://dx.doi.org/10.1038/nrc1951] [PMID: 16990858]
[14]
Nejabat, M.; Soltani, F.; Alibolandi, M.; Nejabat, M.; Abnous, K.; Hadizadeh, F.; Ramezani, M. Smac peptide and doxorubicin-encapsulated nanoparticles: Design, preparation, computational molecular approach and in vitro studies on cancer cells. J. Biomol. Struct. Dyn., 2022, 40(2), 807-819.
[http://dx.doi.org/10.1080/07391102.2020.1819420] [PMID: 32912085]
[15]
Eisvand, F.; Imenshahidi, M.; Ghasemzadeh, R.M.; Tabatabaei, Y.S.A.; Rameshrad, M.; Razavi, B.M.; Hosseinzadeh, H. Cardioprotective effects of alpha‐mangostin on doxorubicin‐induced cardiotoxicity in rats. Phytother. Res., 2022, 36(1), 506-524.
[http://dx.doi.org/10.1002/ptr.7356] [PMID: 34962009]
[16]
Khademi, Z.; Lavaee, P.; Ramezani, M.; Alibolandi, M.; Abnous, K.; Taghdisi, S.M. Co-delivery of doxorubicin and aptamer against Forkhead box M1 using chitosan-gold nanoparticles coated with nucleolin aptamer for synergistic treatment of cancer cells. Carbohydr. Polym., 2020, 248, 116735.
[http://dx.doi.org/10.1016/j.carbpol.2020.116735] [PMID: 32919550]
[17]
Horita, N.; Yamamoto, M.; Sato, T.; Tsukahara, T.; Nagakura, H.; Tashiro, K.; Shibata, Y.; Watanabe, H.; Nagai, K.; Inoue, M.; Nakashima, K.; Ushio, R.; Shinkai, M.; Kudo, M.; Kaneko, T. Topotecan for relapsed small-cell lung cancer: Systematic review and meta-analysis of 1347 patients. Sci. Rep., 2015, 5(1), 15437.
[http://dx.doi.org/10.1038/srep15437] [PMID: 26486755]
[18]
de Man, F.M.; Goey, A.K.L.; van Schaik, R.H.N.; Mathijssen, R.H.J.; Bins, S. Individualization of irinotecan treatment: A review of pharmacokinetics, pharmacodynamics, and pharmacogenetics. Clin. Pharmacokinet., 2018, 57(10), 1229-1254.
[http://dx.doi.org/10.1007/s40262-018-0644-7] [PMID: 29520731]
[19]
Oh, I.J.; Kim, K.S.; Park, C.K.; Kim, Y.C.; Lee, K.H.; Jeong, J.H.; Kim, S.Y.; Lee, J.E.; Shin, K.C.; Jang, T.W.; Lee, H.K.; Lee, K.Y.; Lee, S.Y. Belotecan/cisplatin versus etoposide/cisplatin in previously untreated patients with extensive-stage small cell lung carcinoma: A multi-center randomized phase III trial. BMC Cancer, 2016, 16(1), 690.
[http://dx.doi.org/10.1186/s12885-016-2741-z] [PMID: 27566413]
[20]
Dickson, M.A.; Schwartz, G.K. Development of cell-cycle inhibitors for cancer therapy. Curr. Oncol., 2009, 16(2), 36-43.
[http://dx.doi.org/10.3747/co.v16i2.428] [PMID: 19370178]
[21]
Williams, G.H.; Stoeber, K. The cell cycle and cancer. J. Pathol., 2012, 226(2), 352-364.
[http://dx.doi.org/10.1002/path.3022] [PMID: 21990031]
[22]
Chiu, C.C.; Chou, H.L.; Chen, B.H.; Chang, K.F.; Tseng, C.H.; Fong, Y.; Fu, T.F.; Chang, H.W.; Wu, C.Y.; Tsai, E.M.; Lin, S.R.; Chen, Y.L. BPIQ, a novel synthetic quinoline derivative, inhibits growth and induces mitochondrial apoptosis of lung cancer cells in vitro and in zebrafish xenograft model. BMC Cancer, 2015, 15(1), 962.
[http://dx.doi.org/10.1186/s12885-015-1970-x] [PMID: 26672745]
[23]
Fulda, S.; Debatin, K-M. Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene, 2006, 25(34), 4798-4811.
[http://dx.doi.org/10.1038/sj.onc.1209608] [PMID: 16892092]
[24]
Ghobrial, I.M.; Witzig, T.E.; Adjei, A.A. Targeting apoptosis pathways in cancer therapy. CA Cancer J. Clin., 2005, 55(3), 178-194.
[http://dx.doi.org/10.3322/canjclin.55.3.178] [PMID: 15890640]
[25]
Alnemri, E.S.; Livingston, D.J.; Nicholson, D.W.; Salvesen, G.; Thornberry, N.A.; Wong, W.W.; Yuan, J. Human ICE/CED-3 protease nomenclature. Cell, 1996, 87(2), 171.
[http://dx.doi.org/10.1016/S0092-8674(00)81334-3] [PMID: 8861900]
[26]
Choi, S.; Singh, S.V. Bax and Bak are required for apoptosis induction by sulforaphane, a cruciferous vegetable-derived cancer chemopreventive agent. Cancer Res., 2005, 65(5), 2035-2043.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-3616] [PMID: 15753404]
[27]
Gervais, F.G.; Xu, D.; Robertson, G.S.; Vaillancourt, J.P.; Zhu, Y.; Huang, J.; LeBlanc, A.; Smith, D.; Rigby, M.; Shearman, M.S.; Clarke, E.E.; Zheng, H.; Van Der Ploeg, L.H.T.; Ruffolo, S.C.; Thornberry, N.A.; Xanthoudakis, S.; Zamboni, R.J.; Roy, S.; Nicholson, D.W. Involvement of caspases in proteolytic cleavage of Alzheimer’s amyloid-β precursor protein and amyloidogenic A β peptide formation. Cell, 1999, 97(3), 395-406.
[http://dx.doi.org/10.1016/S0092-8674(00)80748-5] [PMID: 10319819]
[28]
Huang, K.; Zhang, J.; O’Neill, K.L.; Gurumurthy, C.B.; Quadros, R.M.; Tu, Y.; Luo, X. Cleavage by caspase 8 and mitochondrial membrane association activate the BH3-only protein Bid during TRAIL-induced apoptosis. J. Biol. Chem., 2016, 291(22), 11843-11851.
[http://dx.doi.org/10.1074/jbc.M115.711051] [PMID: 27053107]
[29]
Porter, A.G.; Jänicke, R.U. Emerging roles of caspase-3 in apoptosis. Cell Death Differ., 1999, 6(2), 99-104.
[http://dx.doi.org/10.1038/sj.cdd.4400476] [PMID: 10200555]
[30]
Salvesen, G.S. Caspases: Opening the boxes and interpreting the arrows. Cell Death Differ., 2002, 9(1), 3-5.
[http://dx.doi.org/10.1038/sj.cdd.4400963] [PMID: 11803369]
[31]
Oltval, Z.N.; Milliman, C.L.; Korsmeyer, S.J. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programed cell death. Cell, 1993, 74(4), 609-619.
[32]
Zhu, L.; Han, M.B.; Gao, Y.; Wang, H.; Dai, L.; Wen, Y.; Na, L.X. Curcumin triggers apoptosis via upregulation of Bax/Bcl-2 ratio and caspase activation in SW872 human adipocytes. Mol. Med. Rep., 2015, 12(1), 1151-1156.
[http://dx.doi.org/10.3892/mmr.2015.3450] [PMID: 25760477]
[33]
Li, H.; Zhu, H.; Xu, C.; Yuan, J. Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell, 1998, 94(4), 491-501.
[http://dx.doi.org/10.1016/S0092-8674(00)81590-1] [PMID: 9727492]
[34]
Sahu, U.; Sidhar, H.; Ghate, P.S.; Advirao, G.M.; Raghavan, S.C.; Giri, R.K. A novel anticancer agent, 8-methoxypyrimido [4′ 5′ 4, 5] thieno (2, 3-b) quinoline-4 (3H)-one induces neuro 2a neuroblastoma cell death through p53-dependent, caspase-dependent and-independent apoptotic pathways. PLoS One, 2013, 8(6), e66430.
[http://dx.doi.org/10.1371/journal.pone.0066430] [PMID: 23824039]
[35]
Balaji, S.; Neupane, R.; Malla, S.; Khupse, R.; Amawi, H.; Kumari, S.; Tukaramrao, D.B.; Chattopadhyay, S.; Ashby, C.R., Jr; Boddu, S.H.S.; Karthikeyan, C.; Trivedi, P.; Raman, D.; Tiwari, A.K. IND-2, a quinoline derivative, inhibits the proliferation of prostate cancer cells by inducing oxidative stress, apoptosis and inhibiting topoisomerase II. Life, 2022, 12(11), 1879.
[http://dx.doi.org/10.3390/life12111879] [PMID: 36431014]
[36]
Zhou, Q.; McCracken, M.A.; Strobl, J.S. Control of mammary tumor cell growth in vitro by novel cell differentiation and apoptosis agents. Breast Cancer Res. Treat., 2002, 75(2), 107-117.
[http://dx.doi.org/10.1023/A:1019698807564] [PMID: 12243503]
[37]
He, R.; Xu, B.; Ping, L.; Lv, X. Structural optimization towards promising β-methyl-4-acrylamido quinoline derivatives as PI3K/mTOR dual inhibitors for anti-cancer therapy: The in vitro and in vivo biological evaluation. Eur. J. Med. Chem., 2021, 214, 113249.
[http://dx.doi.org/10.1016/j.ejmech.2021.113249] [PMID: 33561608]

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