Login Register Cart 0
Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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

Synthesis and Biological Evaluation of New 1,2,3-Triazole Derivatives of the Chrysin Flavonoid as Anticancer Agents

Author(s): Venkatagiri Noole, Thotla Krishna, Sudhakar Godeshala, Seyedehmelika Meraji, Kaushal Rege, Chepyala K. Reddy* and Bhavani Kedika*

Volume 22, Issue 1, 2022

Published on: 15 March, 2021

Page: [160 - 168] Pages: 9

DOI: 10.2174/1871520621666210315090527

Price: $65

Abstract

Background and Objective: Chrysin and its derivatives proved to possess potential anti-tumour activity.

Materials and Methods: A new series of chrysin analogs containing 1,2,3-triazoles with different substituent groups (5a-5l) was designed, synthesized, and evaluated as potential anticancer agents. The synthesized compounds were characterized using FT-IR, 1H NMR 13C NMR spectroscopy and mass spectrometry.

Results: The anticancer activities of the synthesized compounds were studied in four cancer cell lines viz. PC3, PC3-PSMA, MCF-7 and UM-UC-3 using doxorubicin as standard. Among all the tested compounds, 5c was found as most active with IC50 value of 10.8 ± 0.04 μM in PC3 cells and 20.53 ± 0.21 μMin MCF-7 cells, respectively. Flow cytometry analyses indicated that synthesized compounds 5a, 5c, and 5h arrested MCF-7 cells at the G2/M phase in a dose-dependent manner.

Conclusion: Chyrsin derivatives could be novel anticancer agents.

Keywords: Chrysin, triazoles, anticancer activity, drug design, QSAR, cell cycle analysis.

« Previous Next »
Graphical Abstract

[1]
Jemal, A.; Bray, F.; Center, M.M.; Ferlay, J.; Ward, E.; Forman, D. Global cancer statistics. CA Cancer J. Clin., 2011, 61(2), 69-90.
[http://dx.doi.org/10.3322/caac.20107] [PMID: 21296855]
[2]
Drews, J. Drug discovery: a historical perspective. Science, 2000, 287(5460), 1960-1964.
[http://dx.doi.org/10.1126/science.287.5460.1960] [PMID: 10720314]
[3]
Cragg, G.M.; Grothaus, P.G.; Newman, D.J. Impact of natural products on developing new anti-cancer agents. Chem. Rev., 2009, 109(7), 3012-3043.
[http://dx.doi.org/10.1021/cr900019j] [PMID: 19422222]
[4]
David, J. Newman.; Gordon, M. Cragg. Natural products as sources of new drugs over the last 25 years. J. Nat. Prod., 2007, 70(3), 461-477.Epub 2007 Feb 20.
[http://dx.doi.org/10.1021/np068054v.] [PMID: 17309302]
[5]
Patridge, E.; Gareiss, P.; Kinch, M.S.; Hoyer, D. An analysis of FDA-approved drugs: natural products and their derivatives. Drug Discov. Today, 2016, 21(2), 204-207.
[http://dx.doi.org/10.1016/j.drudis.2015.01.009] [PMID: 25617672]
[6]
David, J. Newman.; Gordon, M. Cragg. Natural Products as Sources of New Drugs from 1981 to 2014. J. Nat. Prod., 2016, 79(3), 629-661.
[http://dx.doi.org/10.1021/acs. jnatprod.5b01055.]
[7]
Heim, K.E.; Tagliaferro, A.R.; Bobilya, D.J. Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. J. Nutr. Biochem., 2002, 13(10), 572-584.
[http://dx.doi.org/10.1016/S0955-2863(02)00208-5] [PMID: 12550068]
[8]
Permender, R.; Hema, C.; Sushila, R.; Dharmender, R.; Vikash, K.; Kanchan, K. Mechanism of action of flavonoids as anti-inflammatory agents: a review. Inflamm. Allergy Drug Targets, 2009, 8(3), 229-235.
[http://dx.doi.org/10.2174/187152809788681029.] [PMID: 19601883. ]
[9]
Priya, Batra Anil, K .Sharma Anti-cancer potential of flavonoids: recent trends and future perspectives. (3 Biotech.)2013, 3(6), 439-459,
[http://dx.doi.org/10.1007/s13205-013-0117-5] [PMID: 28324424]
[10]
Kandaswami, C.; Lee, L.T.; Lee, P.P.; Hwang, J.J.; Ke, F.C.; Huang, Y.T.; Lee, M.T. The antitumor activities of flavonoids. In Vivo, 2005, 19(5), 895-909.
[PMID: 16097445]
[11]
Amany, K.I.; Ahmed, I.Y.; Abdel, S.A.; Safwat, A.A. Anti-H5N1 virus flavonoids from Capparis sinaica Veill. Nat. Prod. Res., 2013, 27(22), 2149-2153.
[http://dx.doi.org/10.1080/14786419.2013.790027.] [PMID: 23651316]
[12]
Ramesh, P.; Sanjeeva Reddy, Ch.; Suresh Babu, K.; Muralidhar Reddy, P.; Srinivasa Rao, V.; Parthasarathy, T. Synthesis, Characterization and Molecular Docking Studies of Novel 2-amino 3-cyano pyrano[2,3H]chrysin Derivatives as Potential Antimicrobial Agents. Med. Chem. Res., 2015, 24(10), 3696-3709.
[http://dx.doi.org/10.1007/s00044-015-1396-7]
[13]
Song, J.H.; Kwon, B.E.; Jang, H.; Kang, H.; Cho, S.; Park, K.; Ko, H.J.; Kim, H. Antiviral Activity of Chrysin Derivatives against Coxsackievirus B3 in vitro and in vivo. Biomol. Ther. (Seoul), 2015, 23(5), 465-470.
[http://dx.doi.org/10.4062/biomolther.2015.095] [PMID: 26336587]
[14]
Yunju, B.; Soyoung, L. Sang-Hyun., Kim. Chrysin suppresses mast cell-mediated allergic inflammation: involvement of calcium, caspase-1 and nuclear factor-Kb. Toxicol. Appl. Pharmacol., 2011, 254(1), 56-64.
[http://dx.doi.org/10.1016/j.taap.2011.04.008.] [PMID: 21515303]
[15]
Wang, J.; Qiu, J.; Dong, J.; Li, H.; Luo, M.; Dai, X.; Zhang, Y.; Leng, B.; Niu, X.; Zhao, S.; Deng, X. Chrysin protects mice from Staphylococcus aureus pneumonia. J. Appl. Microbiol., 2011, 111(6), 1551-1558.
[http://dx.doi.org/10.1111/j.1365-2672.2011.05170.x] [PMID: 21972890]
[16]
Sathiavelu, J.; Senapathy, G.J.; Devaraj, R.; Namasivayam, N. Hepatoprotective effect of chrysin on prooxidant-antioxidant status during ethanol-induced toxicity in female albino rats. J. Pharm. Pharmacol., 2009, 61(6), 809-817.
[http://dx.doi.org/10.1211/jpp.61.06.0015] [PMID: 19505373]
[17]
Zhu, Z.Y.; Wang, W.X.; Wang, Z.Q.; Chen, L.J.; Zhang, J.Y.; Liu, X.C.; Wu, S.P.; Zhang, Y.M. Synthesis and antitumor activity evaluation of chrysin derivatives. Eur. J. Med. Chem., 2014, 75, 297-300.
[http://dx.doi.org/10.1016/j.ejmech.2013.12.044] [PMID: 24556144]
[18]
Song, X.; Liu, Y.; Ma, J. Synthesis of novel amino acid derivatives containing chrysin as anti-tumor agents against human gastric carcinoma MGC-803 cells. Med. Chem. Res., 2015, 24, 1789-1798.
[http://dx.doi.org/10.1007/s00044-014-1267-7]
[19]
Mistry, B.M.; Patel, R.V.; Keum, Y.S.; Kim, D.H. Chrysin-benzothiazole conjugates as antioxidant and anticancer agents. Bioorg. Med. Chem. Lett., 2015, 25(23), 5561-5565.
[http://dx.doi.org/10.1016/j.bmcl.2015.10.052] [PMID: 26514745]
[20]
Patel, R.V.; Mistry, B.; Syed, R.; Rathi, A.K.; Lee, Y.J.; Sung, J.S.; Shinf, H.S.; Keum, Y.S. Chrysin-piperazine conjugates as antioxidant and anticancer agents. Eur. J. Pharm. Sci., 2016, 88(10), 166-177.
[http://dx.doi.org/10.1016/j.ejps.2016.02.011] [PMID: 26924226]
[21]
Karthikeyan, S.; Srinivasan, R.; Wani, S.A.; Manoharan, S. Chemopreventive potential of chrysin in 7, 12-dimethylbenz (a) anthracene-induced hamster buccal pouch carcinogenesis. Int. J. Nutr. Pharmacol. Neurol. Dis, 2013, 3, 46-53.
[http://dx.doi.org/10.4103/2231-0738.106993]
[22]
Ghassan, M. Sulaiman.; Majid, S. Jabir.; Anaheed, H. H. Nanoscale modification of chrysin for improved of therapeutic efficiency and cytotoxicity. Artif. Cells Nanomed. Biotechnol., 2017, 46, 708-720.
[23]
Tsuji, P.A.; Walle, T. Cytotoxic effects of the dietary flavones chrysin and apigenin in a normal trout liver cell line. Chem. Biol. Interact., 2008, 171(1), 37-44.
[http://dx.doi.org/10.1016/j.cbi.2007.08.007] [PMID: 17884029]
[24]
Zheng, H.; Li, S.; Pu, Y.; Lai, Y.; He, B.; Gu, Z. Nanoparticles generated by PEG-Chrysin conjugates for efficient anticancer drug delivery. Eur. J. Pharm. Biopharm., 2014, 87(3), 454-460.
[http://dx.doi.org/10.1016/j.ejpb.2014.03.011] [PMID: 24691159]
[25]
Shaveta; Mishra, S.; Singh, P. Hybrid molecules: The privileged scaffolds for various pharmaceuticals. Eur. J. Med. Chem., 2016, 124, 500-536.
[http://dx.doi.org/10.1016/j.ejmech.2016.08.039] [PMID: 27598238]
[26]
Cláudio, Viegas-Junior.; Amanda, D.; Vanderlan da, S. B. Molecular hybridization: a useful tool in the design of new drug prototypes. Curr. Med. Chem., 2007, 14(17), 1829-1852.
[http://dx.doi.org/10.2174/092986707781058805.] [PMID: 17627520]
[27]
He, Y-W.; Dong, C-Z.; Zhao, J-Y.; Ma, L-L.; Li, Y-H.; Aisa, H.A. 1,2,3-Triazole-containing derivatives of rupestonic acid: click-chemical synthesis and antiviral activities against influenza viruses. Eur. J. Med. Chem., 2014, 76, 245-255.
[http://dx.doi.org/10.1016/j.ejmech.2014.02.029] [PMID: 24583605]
[28]
Ulloora, S.; Shabaraya, R.; Adhikari, A.V. Facile synthesis of new imidazo[1,2-a]pyridines carrying 1,2,3-triazoles via click chemistry and their antiepileptic studies. Bioorg. Med. Chem. Lett., 2013, 23(11), 3368-3372.
[http://dx.doi.org/10.1016/j.bmcl.2013.03.086] [PMID: 23623419]
[29]
Kaushik, C.P.; Lal, K.; Kumar, A.; Kumar, S. Synthesis and biological evaluation of amino acid-linked 1, 2, 3-bistriazole conjugates as potential antimicrobial agents. Med. Chem. Res., 2014, 23(6), 2995-3004.
[http://dx.doi.org/10.1007/s00044-013-0882-z]
[30]
a)Darandale, S. N.; Mulla, N.A.; Pansare, D.N.; Sangshetti, J.N.; Shinde, D.B. A novel amalgamation of 1,2,3-triazoles, piperidines and thieno pyridine rings and evaluation of their antifungal activity. Eur. J. Med. Chem., 2013, 65, 27-532.,
[http://dx.doi.org/10.1016/j.ejmech.2013.04.045]
bDürüst, Y.; Karakuş, H.; Kaiser, M.; Tasdemir, D. Synthesis and anti-protozoal activity of novel dihydropyrrolo[3,4-d][1,2,3]triazoles. Eur. J. Med. Chem., 2012, 48, 296-304.
[http://dx.doi.org/10.1016/j.ejmech.2011.12.028] [PMID: 22217867]
[31]
Mady, M.F.; Awad, G.E.; Jørgensen, K.B. Ultrasound-assisted synthesis of novel 1,2,3-triazoles coupled diaryl sulfone moieties by the CuAAC reaction, and biological evaluation of them as antioxidant and antimicrobial agents. Eur. J. Med. Chem., 2014, 84, 433-443.
[http://dx.doi.org/10.1016/j.ejmech.2014.07.042] [PMID: 25038485]
[32]
Abuo-Rahma, Gel-D.; Abdel-Aziz, M.; Farag, N.A.; Kaoud, T.S. Novel 1-[4-(Aminosulfonyl)phenyl]-1H-1,2,4-triazole derivatives with remarkable selective COX-2 inhibition: design, synthesis, molecular docking, anti-inflammatory and ulcerogenicity studies. Eur. J. Med. Chem., 2014, 83, 398-408.
[http://dx.doi.org/10.1016/j.ejmech.2014.06.049] [PMID: 24983538]
[33]
Pokhodylo, N.; Shyyka, O.; Matiychuk, V. Synthesis of 1,2,3-Triazole Derivatives and Evaluation of their Anticancer Activity. Sci. Pharm., 2013, 81(3), 663-676.
[http://dx.doi.org/10.3797/scipharm.1302-04] [PMID: 24106665]
[34]
Elamari, H.; Slimi, R.; Chabot, G.G.; Quentin, L.; Scherman, D.; Girard, C. Synthesis and in vitro evaluation of potential anticancer activity of mono- and bis-1,2,3-triazole derivatives of bis-alkynes. Eur. J. Med. Chem., 2013, 60, 360-364.
[http://dx.doi.org/10.1016/j.ejmech.2012.12.025] [PMID: 23314049]
[35]
Panda, A.K. Regioselectivity in Benzylation of Chyrsin Asian. J. Chem., 2009, 21(6), 4856-4806.
[36]
Miryala, B.; Godeshala, S.; Grandhi, T.S.; Christensen, M.D.; Tian, Y.; Rege, K. Aminoglycoside-derived amphiphilic nanoparticles for molecular delivery. Colloids Surf. B Biointerfaces, 2016, 146, 924-937.
[http://dx.doi.org/10.1016/j.colsurfb.2016.06.028] [PMID: 27472455]

Rights & Permissions Print Cite
Article Metrics
21
4
© 2024 Bentham Science Publishers | Privacy Policy