Synthesis of Chalcone Derivatives and Their  in vitro  Anticancer Test Against Breast (T47D) and Colon (WiDr) Cancer Cell Line

Chairil Anwar; Yogo Dwi Prasetyo; Sabirin Matsjeh; Winarto Haryadi; Eti Nurwening Sholikhah; Nendrowati Nendrowati

doi:10.22146/ijc.26864

Synthesis of Chalcone Derivatives and Their in vitro Anticancer Test Against Breast (T47D) and Colon (WiDr) Cancer Cell Line

https://doi.org/10.22146/ijc.26864

Chairil Anwar^(1*), Yogo Dwi Prasetyo⁽²⁾, Sabirin Matsjeh⁽³⁾, Winarto Haryadi⁽⁴⁾, Eti Nurwening Sholikhah⁽⁵⁾, Nendrowati Nendrowati⁽⁶⁾

(1) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Jl. Sekip Utara, Yogyakarta 55281, Indonesia
(2) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Jl. Sekip Utara, Yogyakarta 55281, Indonesia
(3) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Jl. Sekip Utara, Yogyakarta 55281, Indonesia
(4) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Jl. Sekip Utara, Yogyakarta 55281, Indonesia
(5) Department of Pharmacology and Therapy, Faculty of Medicine, Universitas Gadjah Mada, Jl. Farmako Sekip Utara, Yogyakarta 55281, Indonesia
(6) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Jl. Sekip Utara, Yogyakarta 55281, Indonesia
(*) Corresponding Author

Abstract

The synthesis of chalcone derivatives as target compounds and anticancer test against breast (T47D) and colon (WiDr) cell line had been performed. The synthesis was performed by Claisen-Schmidt condensation by using acetophenone and benzaldehyde derivatives. The anticancer activity test of chalcone derivatives was carried out by MTT assay against T47D and WiDr cell lines. The synthesis was started by reacting 4-hydroxyacetophenone and benzaldehyde derivatives such as p-anisaldehyde (chalcone A [(E)-4'-hydroxy-4-methoxychalcone]), veratraldehyde (chalcone B [(E)-4'-hydroxy-3,4-dimethoxychalcone]), 4-chlorobenzaldehyde (chalcone C [(E)-4'-hydroxy-4-chlorochalcone]) and 2,4-dihydroxyacetophenone with 4-chlorobenzaldehyde (chalcone D [(E)-2',4'-dihydroxy-4-chlorochalcone]) in methanol as solvent. The synthesis was carried out in alkaline condition (KOH) by stirring the mixture at room temperature for 48 h. The structures of products were identified by FTIR, GC-MS, ¹H- and ¹³C-NMR spectrometers. The results showed that the chalcone derivatives (A-D) were yielded in 96; 97; 96; and 93%, respectively as yellow solid. The anticancer test indicated that the chalcone D was the most active towards T47D cell line with IC₅₀ of 42.66 μg/mL and the chalcone C was the most active against WiDr cell line with IC₅₀ of 20.42 μg/mL.

Keywords

chalcone derivatives; anticancer; breast cancer; colon cancer

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References

[1] King, R.J., 2000, Cancer Biology, 2^nd ed., Pearson Education Limited, London.

[2] Patel, K., Karthikeyan, C., Solomon, V.R., Moorthy, N.S.H.N., Lee, H., Sahu, K., Deora, G.S., and Trivedi, P., 2011, Synthesis of some coumarinyl chalcones and their antiproliferative activity against breast cancer cell lines, Lett. Drug Des. Discovery, 8 (4), 308–311.

[3] World Health Organization, Cancer: Fact sheet February 2017, http://www.who.int/entity/mediacentre/factsheets/fs297/en/index.html, accessed on May 18, 2017.

[4] Kementerian Kesehatan RI, Situasi Penyakit Kanker, http://www.pusdatin.kemkes.go.id/folder/view/01/structure-publikasi-pusdatin-info-datin.html, accessed on May 18, 2017.

[5] Lockshin, R.A., and Zakeri, Z., 2007, Cell death in health and disease, J. Cell. Mol. Med., 11 (6), 1214–1224.

[6] Ranjit, P.M., Rahaman, S.A., Kumar, K.P., Prasad, Y.R., Santhipriya, T., Manikanta, G.C.V.S., and Sudeepthi, N.R.L., 2013, Synthesis, screening and in vitro anticancer activity of piperazine nucleus containing novel chalcones on different cell lines, Int. J. PharmTech Res., 5 (1), 284–293.

[7] Kamuhabwa, A., Nashimo, C., and de Witte, P., 2000, Cytotoxicity of some medicinal plant extracts used in Tanzanian traditional medicine, J. Ethnopharmacol., 70 (2), 143–149.

[8] Li, Y.P., Yang, Y.C., Li, Y.K., Jiang, Z.Y., Huang, X.Z., Wang, W.G., Gao, X.M., and Hu, Q.F., 2014, Prenylated chalcones from Desmodium renifolium, Phytochem. Lett., 9, 41–45.

[9] Patil, C.B., Mahajan, S.K., and Katti, S.A., 2009, Chalcone: A versatile molecule, J. Pharm. Sci. Res., 1 (13), 11–12.

[10] Loudon, M., 2010, Aldol Condensation: Synthesis of Chalcone. Reading: Organic Chemistry, University of Colorado, Colorado.

[11] Zenger, K., Dutta, S., and Genton, M.G., 2015, In vitro structure-toxicity relationship of chalcones in human hepatic stellate cells, Toxicology, 336, 26–33.

[12] Mai, C.W., Yaeghoobi, M., Abd-Rahman, N., Kang, Y.B., and Pichika, M.R., 2014, Chalcones with electron-with drawing and electron-donating substituents: anticancer activity against TRAIL resistant cancer cells, structure-activity relationship analysis, and regulation of apoptotic protein, Eur. J. Med. Chem., 77, 378–387.

[13] Suwito, H., Jumina, J., Mustofa, M., Ni’matuzahroh, N., and Puspaningsih, N.N.T., 2015, Anticancer and antimicrobial activity of methoxy amino chalcone derivatives, Pharma Chem., 7 (3), 89–94.

[14] Zhang, J., Ji, F.J., Gu, Y., Zhang, X.Y., and Qiao, S.X., 2014, Chalcones derivatives as potent cell division cycle 25B phosphatase inhibitors, Pharmacol. Rep., 66 (3), 515–519.

[15] Sultan, A., Raza, A.R., Khan, K.M., Tahir, M.N., and Saari, N., 2013, Evaluation of silica-H₂SO₄ as an efficient heterogeneous catalyst for the synthesis of chalcones, Molecules, 18 (8), 10081–10094.

[16] Susanti, E., Matsjeh, S., Mustofa, and Wahyuningsih, T.D., 2014, Improved synthesis of 2’,6’-dihydroxy-3,4-dimethoxy chalcone by grinding technique to synthesize 5-hydroxy-3’,4’-dimethoxyflavone, Indones. J. Chem., 14 (2), 174–178.

[17] Hsieh, C.T., Hsieh, T.J., El-Shazly, M., Chuang, D.W., Tsai, Y.H., Yen, C.T., Wu, S.E., Wu, Y.C., and Chang, F.R., 2012, Synthesis of chalcone derivatives as potential anti-diabetic agents, Bioorg. Med. Chem. Lett., 22 (12), 3912–3915.

[18] Narender, T., and Reddy, K.P., 2007, A simple and highly efficient method for the synthesis of chalcones by using borontrifluoride-etherate, Tetrahedron. Lett., 48 (18), 3177–3180.

[19] Akhtar, M.N., Sakeh, N.M., Zareen, S., Gul, S., Lo, M.K., Ul-Haq, Z., Shak, S.A.A., and Ahmad, S., 2014, Design and synthesis of chalcone derivatives as potent tyrosinase inhibitors and their structural activity relationship, J. Mol. Struct., 1085, 97–103.

[20] Pavia, D.L., Lampman, G.M., Kriz, G.S., and Vyvyan, J.R., 2009, Introduction to Spectroscopy, 4^thed., Brooks/Cole Cengage Learning, Belmont.

[21] Tran, T.D., Nguyen, T.T., Do, T.H., Huynh, T.N., Tran, C.D., and Thai, K.M., 2012, Synthesis and antibacterial activity of some heterocyclic chalcone analogues alone and in combination with antibiotics, Molecules, 17 (6), 6684–6696.

[22] Tanamatarayat, P., Chunsakaow, S., and Duangrat, C., 2003, Screening of some rubiaceous plants for cytotoxicity activity against cervix carcinoma (KB-3-1) cell line, J. Pharm. Sci., 27(3-4), 167–172.

[23] Ketabforoosh, S.H.M.E., Kheirollahi, A., Safavi, M., Esmati, N., Ardestani, S.K., Emami, S., Firoozpour, L., Shafiee, A., and Foroumadi, A., 2014, Synthesis and anti-cancer activity evaluation of new dimethoxylated chalcone and flavanone analogs, Arch. Pharm., 347 (11), 853–860.

DOI: https://doi.org/10.22146/ijc.26864