Login Register Cart 0
Generic placeholder image

Letters in Drug Design & Discovery

Editor-in-Chief

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

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Acenaphthotriazine Thio-triazole Derivatives as Anti-cancer Agents Triggering Cell Cycle Arrest in Breast Cancer Cells

Author(s): Aida Iraji, Nasim Shahrokh, Omidreza Firuzi, Maryam Mohabbati, Ramin Miri, Hossein Sadeghpour, Mehdi Khoshneviszadeh* and Najmeh Edraki*

Volume 20, Issue 6, 2023

Published on: 30 June, 2022

Page: [639 - 648] Pages: 10

DOI: 10.2174/1570180819666220425123016

Price: $65

Abstract

Background: Cancer is one of the most devastating diseases, affecting the lives of millions of people around the world.

Introduction: A series of acenaphtho[1,2-e][1,2,4]triazine containing different thiomethyl-1,2,3-triazole derivatives were designed based on a fragment-based and molecular hybridization approach as anti-cancer agents.

Methods: Designed compounds were synthesized using cycloaddition condensation followed by click reaction. Cytotoxicity of prepared compounds was evaluated by MTT reduction assay against four different cancer cell lines.

Results: The biological evaluation indicated that derivative 6d with para-fluorobenzyl moiety was the most active cytotoxic agent with IC50 values of 70.1, 12.8, 41.5, and 16.0 μM against K562, MOLT-4, HT-29, and MCF-7 cells, respectively. Cell cycle analysis showed that acenaphtho triazine derivatives could induce G0/G1 phase arrest in MCF-7 breast cancer cells.

Conclusion: Synthesized derivatives can be ideal candidates for further exploration as anti-cancer agents.

Keywords: Anti-cancer effect, cell cycle, click chemistry, acenaphtho triazine triazole, derivatives, cycloaddition condensation.

« Previous Next »
Graphical Abstract

[1]
Adibi Sedeh, S.; Mohammadi, M.K.; Fereidoonnezhad, M.; Javid, A. Synthesis and anticancer evaluation of novel acenaphtho [1, 2-e]-1, 2, 4-triazine derivatives Iranian. Chem. Commun. (Camb.), 2019, 7, 521-528.
[2]
Bahia, M.T.; de Andrade, I.M.; Martins, T.A.; do Nascimento, Á.F.; Diniz, Lde.F.; Caldas, I.S.; Talvani, A.; Trunz, B.B.; Torreele, E.; Ribeiro, I. Fexinidazole: A potential new drug candidate for Chagas disease. PLoS Negl. Trop. Dis., 2012, 6(11)e1870
[http://dx.doi.org/10.1371/journal.pntd.0001870] [PMID: 23133682]
[3]
Cardoso, M.F.C.; Rodrigues, P.C.; Oliveira, M.E.; Gama, I.L.; da Silva, I.M.; Santos, I.O.; Rocha, D.R.; Pinho, R.T.; Ferreira, V.F.; de Souza, M.C.; da Silva, Fde.C.; Silva, F.P. Jr Synthesis and evaluation of the cytotoxic activity of 1,2-furanonaphthoquinones tethered to 1,2,3-1H-triazoles in myeloid and lymphoid leukemia cell lines. Eur. J. Med. Chem., 2014, 84, 708-717.
[http://dx.doi.org/10.1016/j.ejmech.2014.07.079] [PMID: 25064348]
[4]
Costa, D.C.S.; de Almeida, G.S.; Rabelo, V.W.; Cabral, L.M.; Sathler, P.C.; Alvarez Abreu, P.; Ferreira, V.F.; Cláudio Rodrigues Pereira da Silva, L.; da Silva, F.C. Synthesis and evaluation of the cytotoxic activity of Furanaphthoquinones tethered to 1H-1,2,3-triazoles in Caco-2, Calu-3, MDA-MB231 cells. Eur. J. Med. Chem., 2018, 156, 524-533.
[http://dx.doi.org/10.1016/j.ejmech.2018.07.018] [PMID: 30025347]
[5]
de Oliveira, C.; Weir, S.; Rangrej, J.; Krahn, M.D.; Mittmann, N.; Hoch, J.S.; Chan, K.K.W.; Peacock, S. The economic burden of cancer care in Canada: A population-based cost study. CMAJ Open, 2018, 6(1), E1-E10.
[http://dx.doi.org/10.9778/cmajo.20170144] [PMID: 29301745]
[6]
Dheer, D.; Singh, V.; Shankar, R. Medicinal attributes of 1,2,3-triazoles: Current developments. Bioorg. Chem., 2017, 71, 30-54.
[http://dx.doi.org/10.1016/j.bioorg.2017.01.010] [PMID: 28126288]
[7]
Dwivedi, P.; Mishra, K.B.; Mishra, B.B.; Singh, N.; Singh, R.K.; Tiwari, V.K. Click inspired synthesis of antileishmanial triazolyl O-benzylquercetin glycoconjugates. Glycoconj. J., 2015, 32(3-4), 127-140.
[http://dx.doi.org/10.1007/s10719-015-9582-x] [PMID: 25869315]
[8]
Gholampour, M.; Ranjbar, S.; Edraki, N.; Mohabbati, M.; Firuzi, O.; Khoshneviszadeh, M. Click chemistry-assisted synthesis of novel aminonaphthoquinone-1,2,3-triazole hybrids and investigation of their cytotoxicity and cancer cell cycle alterations. Bioorg. Chem., 2019, 88102967
[http://dx.doi.org/10.1016/j.bioorg.2019.102967] [PMID: 31078767]
[9]
Iraji, A.; Firuzi, O.; Khoshneviszadeh, M.; Tavakkoli, M.; Mahdavi, M.; Nadri, H.; Edraki, N.; Miri, R. Multifunctional iminochromene-2H-carboxamide derivatives containing different aminomethylene triazole with BACE1 inhibitory, neuroprotective and metal chelating properties targeting Alzheimer’s disease. Eur. J. Med. Chem., 2017, 141, 690-702.
[http://dx.doi.org/10.1016/j.ejmech.2017.09.057] [PMID: 29107423]
[10]
Jadhav, R.P.; Raundal, H.N.; Patil, A.A.; Bobade, V.D. Synthesis and biological evaluation of a series of 1, 4-disubstituted 1, 2, 3-triazole derivatives as possible antimicrobial agents. J. Saudi Chem. Soc., 2017, 21, 152-159.
[http://dx.doi.org/10.1016/j.jscs.2015.03.003]
[11]
Jia, Y.; Si, L.; Lin, R.; Jin, H.; Jian, W.; Yu, Q.; Yang, S. Thiophenol-formaldehyde triazole causes apoptosis induction in ovary cancer cells and prevents tumor growth formation in mice model. Eur. J. Med. Chem., 2019, 172, 62-70.
[http://dx.doi.org/10.1016/j.ejmech.2019.03.033] [PMID: 30947122]
[12]
Kim, T.W.; Yong, Y.; Shin, S.Y.; Jung, H.; Park, K.H.; Lee, Y.H.; Lim, Y.; Jung, K.Y. Synthesis and biological evaluation of phenyl-1H-1,2,3-triazole derivatives as anti-inflammatory agents. Bioorg. Chem., 2015, 59, 1-11.
[http://dx.doi.org/10.1016/j.bioorg.2015.01.003] [PMID: 25658192]
[13]
Liu, F.; Qian, X.; Cui, J.; Xiao, Y.; Zhang, R.; Li, G. Design, synthesis, and antitumor evaluation of novel acenaphtho[1,2-b]pyrrole-carboxylic acid esters with amino chain substitution. Bioorg. Med. Chem., 2006, 14(13), 4639-4644.
[http://dx.doi.org/10.1016/j.bmc.2006.02.016] [PMID: 16516477]
[14]
Mavrova, A.Ts.; Wesselinova, D.; Tsenov, Y.A.; Denkova, P. Synthesis, cytotoxicity and effects of some 1,2,4-triazole and 1,3,4-thiadiazole derivatives on immunocompetent cells. Eur. J. Med. Chem., 2009, 44(1), 63-69.
[http://dx.doi.org/10.1016/j.ejmech.2008.03.006] [PMID: 18439727]
[15]
Mohammadi, M.K.; Firuzi, O.; Khoshneviszadeh, M.; Razzaghi-Asl, N.; Sepehri, S.; Miri, R. Novel 9-(alkylthio)-Acenaphtho [1, 2-e]-1, 2, 4-triazine derivatives: Synthesis, cytotoxic activity and molecular docking studies on B-cell lymphoma 2 (Bcl-2). DARU. J. Pharm. Sci., 2014, 22(1), 11.
[http://dx.doi.org/10.1186/2008-2231-22-2] [PMID: 24393539]
[16]
Ruddarraju, R.R.; Murugulla, A.C.; Kotla, R.; Chandra Babu Tirumalasetty, M.; Wudayagiri, R.; Donthabakthuni, S.; Maroju, R.; Baburao, K.; Parasa, L.S. Design, synthesis, anticancer, antimicrobial activities and molecular docking studies of theophylline containing acetylenes and theophylline containing 1,2,3-triazoles with variant nucleoside derivatives. Eur. J. Med. Chem., 2016, 123, 379-396.
[http://dx.doi.org/10.1016/j.ejmech.2016.07.024] [PMID: 27487568]
[17]
Sarigol, D.; Uzgoren-Baran, A.; Tel, B.C.; Somuncuoglu, E.I.; Kazkayasi, I.; Ozadali-Sari, K.; Unsal-Tan, O.; Okay, G.; Ertan, M.; Tozkoparan, B. Novel thiazolo[3,2-b]-1,2,4-triazoles derived from naproxen with analgesic/anti-inflammatory properties: Synthesis, biological evaluation and molecular modeling studies. Bioorg. Med. Chem., 2015, 23(10), 2518-2528.
[http://dx.doi.org/10.1016/j.bmc.2015.03.049] [PMID: 25868745]
[18]
Sayeed, I.B.; Vishnuvardhan, M.V.P.S.; Nagarajan, A.; Kantevari, S.; Kamal, A. Imidazopyridine linked triazoles as tubulin inhibitors, effectively triggering apoptosis in lung cancer cell line. Bioorg. Chem., 2018, 80, 714-720.
[http://dx.doi.org/10.1016/j.bioorg.2018.07.026] [PMID: 30075408]
[19]
Siegel, R.L.; Miller, K.D.; Fuchs, H.E.; Jemal, A. Cancer statistics. Cancer J. Clin., 2021, 71, 7-33.
[http://dx.doi.org/10.3322/caac.21654]
[20]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics. Cancer J. Clin., 2019, 69, 7-34.
[http://dx.doi.org/10.3322/caac.21551]
[21]
Silva Júnior, ENd Cytotoxic, trypanocidal activities and physicochemical parameters of nor-2-lapachone-based 1, 2, 3-triazoles. J. Braz. Chem. Soc., 2009, 20, 635-643.
[http://dx.doi.org/10.1590/S0103-50532009000400007]
[22]
Xie, L.; Xiao, Y.; Wang, F.; Xu, Y.; Qian, X.; Zhang, R.; Cui, J.; Liu, J. Novel acenaphtho[1,2-b]pyrrole-carboxylic acid family: Synthesis, cytotoxicity, DNA-binding and cell cycle evaluation. Bioorg. Med. Chem., 2009, 17(21), 7615-7621.
[http://dx.doi.org/10.1016/j.bmc.2009.02.031] [PMID: 19815418]
[23]
Yazdani, M.; Edraki, N.; Badri, R.; Khoshneviszadeh, M.; Iraji, A.; Firuzi, O. 5,6-Diphenyl triazine-thio methyl triazole hybrid as a new Alzheimer’s disease modifying agents. Mol. Divers., 2020, 24(3), 641-654.
[http://dx.doi.org/10.1007/s11030-019-09970-3] [PMID: 31327094]
[24]
Yazdani, M.; Edraki, N.; Badri, R.; Khoshneviszadeh, M.; Iraji, A.; Firuzi, O. Multi-target inhibitors against Alzheimer disease derived from 3-hydrazinyl 1,2,4-triazine scaffold containing pendant phenoxy methyl-1,2,3-triazole: Design, synthesis and biological evaluation. Bioorg. Chem., 2019, 84, 363-371.
[http://dx.doi.org/10.1016/j.bioorg.2018.11.038] [PMID: 30530107]
[25]
Zhang, Z.; Song, T.; Li, X.; Wu, Z.; Feng, Y.; Xie, F.; Liu, C.; Qin, J.; Chen, H. Novel soluble myeloid cell leukemia sequence 1 (Mcl-1) inhibitor (E,E)-2-(benzylaminocarbonyl)-3-styrylacrylonitrile (4g) developed using a fragment-based approach. Eur. J. Med. Chem., 2013, 59, 141-149.
[http://dx.doi.org/10.1016/j.ejmech.2012.10.050] [PMID: 23220642]
[26]
Zhang, Z.; Wu, G.; Xie, F.; Song, T.; Chang, X. 3-Thiomorpholin-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile (S1) based molecules as potent, dual inhibitors of B-cell lymphoma 2 (Bcl-2) and myeloid cell leukemia sequence 1 (Mcl-1): Structure-based design and structure-activity relationship studies. J. Med. Chem., 2011, 54(4), 1101-1105. a
[http://dx.doi.org/10.1021/jm101181u] [PMID: 21235240]
[27]
Zhang, Z.; Yang, H.; Wu, G.; Li, Z.; Song, T.; Li, X.Q. Probing the difference between BH3 groove of Mcl-1 and Bcl-2 protein: Implications for dual inhibitors design. Eur. J. Med. Chem., 2011, 46(9), 3909-3916.
[http://dx.doi.org/10.1016/j.ejmech.2011.05.062] [PMID: 21684048]

Rights & Permissions Print Cite
Article Metrics
25
2
© 2024 Bentham Science Publishers | Privacy Policy