Synthesis and Cytotoxic Test of Halogen-Substituted Chalcone Against MCF-7 Breast Cancer Cells

Eti Meirina Brahmana; Jamaran Kaban; Ginda Haro; Mimpin Ginting

doi:10.22146/ijc.69991

Synthesis and Cytotoxic Test of Halogen-Substituted Chalcone Against MCF-7 Breast Cancer Cells

https://doi.org/10.22146/ijc.69991

Eti Meirina Brahmana⁽¹⁾, Jamaran Kaban^(2*), Ginda Haro⁽³⁾, Mimpin Ginting⁽⁴⁾

(1) Postgraduate School, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Sumatera Utara, Jl. Bioteknologi No. 1, Medan 20155, Indonesia; Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Sumatera Utara, Jl. Bioteknologi No. 1, Medan 20155, Indonesia; Biology Study Program, Faculty of Teaching Training and Education, Universitas Pasir Pengaraian, Riau 28557, Indonesia
(2) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Sumatera Utara, Jl. Bioteknologi No. 1, Medan 20155, Indonesia
(3) Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Sumatera Utara, Jl. Tri Dharma No. 5, Medan 20155, Indonesia
(4) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Sumatera Utara, Jl. Bioteknologi No. 1, Medan 20155, Indonesia
(*) Corresponding Author

Abstract

A series of chalcones was synthesized to be (E)-1-(4-chlorophenyl)-3-p-tolyprop-2-en-1-on (1), (E)-1-(4-chlorophenyl)-3-(4-tolyprophenyl) prop-2-en-1-on (2), (E)-1-(3-bromophenyl)-3-p-tolylprop-2-en-1-on (3), and (E)-1-(3-bromophenyl)-3-(4-isopropyl phenyl) prop-2-en-1-on (4) using irradiate microwave method with reaction time from 3, 6, and 8 min at 800 °C and 700 W. The compounds were characterized using TLC, UV-Vis, FTIR, ¹H-NMR, and evaluated MCF-7 cancer cell cytotoxic test with Presto BlueTM. All compounds produced were in the form of yellow crystals. The results showed that compounds 2, 3, and 4 were potentially a Como prevention agent and inhibit cell proliferation with IC₅₀ values of 37.24, 422.22, and 22.41 ppm, respectively. While compound 1 had IC₅₀ 1,484.75 and no cytotoxic effect. Further tests should be carried out for compounds 2, 3, and 4 against normal cells to measure the compound's safety for normal cells.

Keywords

breast cancer; chalcones; MCF-7 cancer cell

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References

[1] Ahmad, M.R., Sastry, V.G., Bano, N., and Anwar, S., 2016, Synthesis of novel derivatives by conventional and microwave irradiation methods and their pharmacological activities, Arabian J. Chem., 9, S931–S935.

[2] Wang, G., Liu, W., Gong, Z., Huang, Y., Li, Y., and Peng, Z., 2019, Design, synthesis, biological evaluation and molecular docking studies of new chalcone derivatives containing diaryl ether moiety as potential anticancer agents and tubulin polymerization inhibitors, Bioorg. Chem., 95, 103565.

[3] Wang, G., Peng, Z., and Li, Y., 2020, Synthesis, anticancer activity and molecular modelling studies of novel chalcone derivatives containing indole and naphthalene moieties as tubulin polymerization inhibitors, Chem. Pharm. Bull., 67 (7), 725–728.

[4] Harmastuti, N., Herowati, R., Susilowati, D., Pranowo, H.D., and Mubarika, S., 2012, Synthesis and cytotoxic activity of chalcone derivatives on human breast cancer cell lines, Indones. J. Chem., 12 (3), 261–267.

[5] Adnan, D., Singh, B., Mehta, S.K., Kumar, V., and Kataria, R., 2020, Simple and solvent free practical procedure for chalcones: An expeditious, mild and greener approach, Curr. Res. Green Sustainable Chem., 3, 100041.

[6] Iqbal, J., Abbasi, B.A., Mahmood, T., Kanwal, S., Ali, B., Shah, S.A., and Khalil, A.T., 2017, Plant-derived anticancer agents: A green anticancer approach, Asian Pac. J. Trop. Biomed., 7 (12), 1129–1150.

[7] World Health Organization, 2018, Latest Global Cancer Data: Cancer Burden Rises to 18.1 Million New Cases and 9.6 Million Cancer Deaths in 2018, World Health Organization, Geneva.

[8] Luo, Y., Wu, W., Zha, D., Zhou, M., Wang, C., Huang, J., Chen, S., Yu, L., Li, Y., Huang, Q., Zhang, J., and Zhang, C., 2021, Synthesis and biological evaluation of novel ligustrazine-chalcone derivatives as potential anti-triplet breast cancer agents, Bioorg. Med. Chem. Lett., 47, 128230.

[9] Anwar, C., Prasetyo, Y.D., Matsjeh, S., Haryadi, W., Sholikhah, E.N., and Nendrowati, N., 2018, Synthesis of chalcone derivatives and their in vitro anticancer test against breast (T47D) and colon (WiDr) cancer cell line, Indones. J. Chem., 18 (1), 102–107.

[10] Brahmana, E.M., Adel, Z., and Hilwan, Y.T., 2013, Sintesis dan uji toksisitas (E)-1-(2-chlorophenyl)-3-p-tolylprop-2-en-1-on, Indones. Chem. Acta, 4 (1), 21–25.

[11] Uddin, M.N., M.Knock, N.H., Uzzaman, M.M.H., Bhuiyyan, M., Sanaullah, A.F.M., Shumi, W., and Sadrul Amin, H.M., 2020, Microwave assisted synthesis, characterization, molecular docking and pharmacological activities of some new 2’-hydrixychalcone derivatives, J. Mol. Struct., 1206, 127678.

[12] Maqsood, M., Qureshi, R., Ikram, M., Ahmad, M.S., Jabeen, B., Asi, M.R., Khan, J.A., Ali, S., and Lilge, L., 2018, In vitro anticancer activities of Withania coagulans against HeLa, MCF-7, RD, RG2, and INS-1 cancer cells and phytochemical analysis, Intergr. Med. Res., 7 (2), 184–191.

[13] Wulandari, L., 2011, Kromatografi Lapis Tipis, PT Taman Kampus Presindo, Jember.

[14] Fesseden, J.S., and Fesseden, R.J., 2010, Dasar-dasar Kimia Organik, PT. Binarupa Aksara, Tangerang.

[15] Kriz, G.S., Lampman, G.M., Vyvyan, J.A., and Pavia, D.L., 2014, Introduction to Spectroscopy, Cengage Learning, US.

[16] Modwi, A., Ali, M.K.M., Taha, K.K., Ibrahem, M.A., El-Khair, H.M., Eisa, M.H., Elamin, M.R., Aldaghri, O., Alhathlool, R., and Ibnaouf, K.H., 2017, Structural and optical characteristic of chalcone doped ZnO nanoparticles, J. Mater. Sci.: Mater. Electron., 29 (4), 2791–2796.

[17] Yadav, V.R., Prasad, S., Sung, B., and Aggarwal, B.B., 2011, The role of chalcones in suppression of NF-κB-mediated inflammation and cancer, Int. Immunopharmacol., 11 (3), 295–309.

[18] Vh, E.S., 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’-dimethyoxy flavone, Indones. J. Chem., 14 (2), 174–178.

[19] National Cancer Institute, 2015, Tumor Markers Fact Sheet, National Cancer Institute US Department of Health and Human Services, Maryland, US.

[20] Meiyanto, E., Putri, D.D.P., Susidarti, R.A., Murwanti, R., Sadjiman, Fitriasari, A., Husnaa, U., Purnomo, H., and Kawaichi, M., 2014, Curcumin and its analogues (PGV-0 and PGV-1) enhance sensitivity of resistant MCF-7 cells to doxorubicin through inhibitions of HER2 and NF-κB activation, Asian Pac. J. Cancer Prev., 15 (1), 179–184.

[21] Zhu, M., Wang, J.B., Xie, J.W., Chen, L.P., Wei, X.Y., and Jiang, X., 2018, Design, synthesis, and evaluation of chalcone analogues incorporate a,b-unsaturated ketone functionality as anti-lung, cancer agents via evoking ROS to induce pyroptosis, Eur. J. Med. Chem., 157, 1395–1405.

[22] Ramos, A., Carvalho, B., Sena, M., Dethoup, T., Buttachon, S., Kijjoa, A., and Rocha, E., 2016, Crude extract of marine-derived and soil fungi of the genus Neosartorya exhibit selective anticancer activity by inducing cell death in colon, breast, and skin cancer cell lines, Pharmacogn. Res., 8 (1), 8–15.

DOI: https://doi.org/10.22146/ijc.69991