Sintesis, Molecular Docking dan Aktivitas Sitotoksik Senyawa Analog Kalkon Berbasis Alfa Tetralone terhadap Sel Kanker Payudara MCF-7
Synthesis, Molecular Docking, and Cytotoxic Activity of Alpha Tetralone Based Chalcone Analogue Compounds against MCF-7 Breast Cancer Cells
DOI:
https://doi.org/10.25026/jsk.v6i1.2092Abstract
The chalcone compound is a precursor of flavonoid and pyrazoline compounds. Chalcone has two aromatic rings (A and B) and one ?,?-unsaturated carbon atom. Chalcone compounds can be synthesized via the Claisen Schmidt condensation reaction. Chalcone synthesis uses the basic ingredients of alpha tetralone and benzaldehyde analogues. In this research, chalcone synthesis took place for 48 hours at room temperature. Synthetic materials using ethanol solvent and sodium hydroxide catalyst, as well as basic ingredients alpha tetralone, 3,4-dimethoxybenzaldehyde and 4-methoxybenzaldehyde. Characterization of synthesized compounds using spectroscopic methods, including 1H-NMR, 13C-NMR, Fourier Transform Infrared (FTIR) and mass spectroscopy. Characterization results using spectroscopic methods showed that the two chalcone analogue compounds were successfully synthesized with yields above 70%. Both chalcone compounds showed low activity against MCF-7 cancer cells. Molecular docking simulations showed that both chalcone analogues produced energy levels and intramolecular interactions that were no better than 4-hydroxytamoxifen.
Keywords: chalcone analogues, alpha tetralone, cytotoxic
Abstrak
Senyawa kalkon merupakan salah satu prekursor dari senyawa flavonoid dan pirazolina. Kalkon mengandung dua cincin aromatis (A dan B) dan satu atom karbon ?,?-tak jenuh. Senyawa kalkon dapat disintesis melalui reaksi kondensasi Claisen Schmidt. Kalkon disintesis menggunakan bahan dasar alfa tetralone dan analog benzaldehida. Dalam penelitian ini senyawa kalkon disintesis selama 48 jam pada suhu ruang menggunakan pelarut etanol dan katalis natrium hidroksida serta bahan dasar alfa tetralone, 3,4-dimetoksibenzaldehida dan 4-metoksibenzaldehida. Senyawa hasil sintesis dikarakterisasi menggunakan metode spektroskopi meliputi 1H-NMR, 13C-NMR, Fourier Transform Infrared (FTIR) dan spektroskopi massa. Karakterisasi menggunakan metode spektroskopi menunjukkan kedua senyawa analog kalkon berhasil disintesis dengan rendemen diatas 70%. Hasil pengujian sitotoksik menunjukkan bahwa kedua senyawa analog kalkon tidak aktif terhadap sel kanker payudara MCF-7. Simulasi penambatan molekuler menunjukkan bahwa kedua analog kalkon menghasilkan tingkat energi dan interaksi intramolekuler yang tidak lebih baik dibandingkan dengan 4-hidroksitamoksifen.
Kata Kunci: analog kalkon, alfa tetralone, sitotoksik
References
Ningrum, M. P. dan Rahayu, RR. S. R. 2021. Determinan Kejadian Kanker Payudara Pada Wanita Usia Subur (15-49) Tahun. Indonesian Journal of Public Health and Nutrition. 1(3). 362-370.
Globocan. 2020. International Agency for Research on Cancer (IARC). 2021. Estimated Number of Deaths in 2020 Worldwide, Indonesia, Female, All Ages.
Qodria, L. dan Nurrachma, M. Y. 2020. Pemilihan Sel yang Tepat Untuk Penelitian Kanker Payudara. BioTrends. 11(2). 17-28.
Goyal, K., Kaur, R., Goyal, A., and Awasthi, R. 2021. Chalcones: A Review On Synthesis and Pharmacological Activities. J. Appl. Pharm. Sci. 11(1). 1-14.
Salehi, B., Quispe, C., Chamki, I., El Omari, N., Balahbib, A., Sharifi-Rad, J., Bouyahya, A., Akram, M., Iqbal, M., Docea, A.O., Caruntu, C., Leyva-Gomez, G., Dey, A., Martorell, M., Calina, D., Lopez, V., and Les, F. 2021. Pharmacological Properties of Chalcones: A Review of Preclinical Including Molecular Mechanism and Clinical Evidence. Front. Pharmacol. 11. 592654.
Khotimah, N., Rahmadani, A., Rahmawati, D., and Ardana, M. 2018. Synthesis and Bioactivity of 3-(2,4-Dichlorophenyl)-5-(4-Hydroxy-3-Methoxyphenyl) Pyrazoline. J. Trop. Pharm. Chem. 4(4). 189-193.
Santi, F, N., Nur, Y., Rahmadani, A, Herman, and Kuncoro, H. 2019. Synthesis and Bioactivity of New Pyrazoline Derivative: N-Carbamide-3-(2,4-Dichlorophenyl)-5-(4-Hydroxy-3-Methoxyphenyl) Pyrazoline. Res. J. Chem. Environ. 23(12). 55-59.
Shidiq, N., Rahmadani, A., Wijaya, V., dan Rijai, L. 2018. Sintesis Senyawa Turunan Flavanon dan Uji Bioaktivitas Senyawa Kalkon sebagai Senyawa Antara dalam Sintesis Flavanon. Proc. Mul. Pharm. Conf. 8(1). 68-74.
Ikhtiarudin, I., Lelani, Zamri, A., Teruna, H.Y., dan Yuharmen. 2014. Sintesis dan Uji Toksisitas Senyawa Analog Kalkon Turunan 2’-Hidroksiasetofenon dan Halobenzaldehid. Jurnal Photon. 5(1). 57- 63.
Fauziah, L. dan Wahyuningsih, T.D. 2016. Synthesis of Chalcones Substituted with Nitro and Hydroxyl Group in Alkaline Medium. Eksakta: Journal of Sciences and Data Analysis. 16(2). 103-114.
Suirta, I. W. 2016. Sintesis Senyawa Kalkon serta Uji Aktivitas Sebagai Antioksidan. Jurnal Kimia. 10(1), 75-80.
Gupta, D and Dain, J. K. 2015. Chalcone Derivates as Potential Antifungal Agents: Synthesis and Antifungal Activity. J. Adv. Pharm. Technol. Res. 6(3). 114-117.
Shirmila, D. A., Jonathan, D. R., KhrisnaPriya, M., Laavanya, K., Hemalatha, J., and Usha, G. 2022. Synthesis, In-vitro and In-silico Antikanker Activity Studies of Methoxy Chalcone Substitued Tetralone-Based Chalcone Derivates. Rasayan J. Chem. 15(4). 2249-2257.
Csizmadia, P. 1999. MarvinSketch and MarvinView: Molecule Applets for the World Wide Web. The 3rd International Electronic Conference on Synthetic Organic Chemistry.
Hanwell, M. D., Curtis, D. E., Lonie, D. C., Vandermeersch, T., Zurek, E., and Hutchison, G. R. 2012. Avogadro: An Advanced Semantic Chemical Editor, Visualization, and Analysis Platform. J. Cheminform. 4(8). 1-17.
Atwell, T. L., Townsend, P. A., and Grayson, M. N. 2021. Comparisons of Different Force Fields in Conformational Analysis and Searching of Organic Molecules: A Review. Tetrahedron. 79. 131865.
Forli, S., Huey, R., Pique, M. E., Sanner, M. F., Goodsell, D. S., and Olson, A. J. 2016. Computational Protein–Ligand Docking and Virtual Drug Screening with the AutoDock Suite. Natureprotocols. 11(5). 905-919.
Aldaghi, L., Rad, A., Arab, A., Kasaian, J., Iranshasi, M., Sadr, A. S., and Soltani, F. 2016. In Silico and In Vitro Evaluation of Cytotoxic Activities of Farnesiferol C and Microlobin on MCF-7, Hela and KYSE Cell Lines. Drug. Res. 66(10). 532-538.
Huey, R., Morris, G. M., and Forli, S. 2012. Using AutoDock 4 and AutoDock Vina with AutoDockTools: A Tutorial. The Scripps Research Institute Molecular Graphics Laboratory. California. USA.
Baroroh, U., Muscipa, Z. S., Destiarani, W., Rahmatullah, F. G., and Yusuf, M. 2023. Molecular Interaction Analysis and Visualization of Protein-Ligand Docking Using Biovia Discovery Studio Visualizer. Indonesian Journal of Computational Biology. 2(1). 22-30.
Wang, Z., Li, Y., Ai, C., and Wang, Y. 2010. In Silico Prediction of Estrogen Receptor Subtype Binding Affinity and Selectivity Using Statistical Methods and Molecular Docking with 2-Arylnaphthalenes and 2-Arylquinolines. Int. J. Mol. Sci. 11(9). 3434–3458.
Shylaja, R., Loganathan, C., Kabilan, S., Vijayakumar, T., and Meganathan, C. 2021. Synthesis and Evaluation of the Antagonistic Activity of 3-acetyl-2H-benzo[g]chromen-2-one Against Mutant Y537S Estrogen Receptor Alpha via E-Pharmacophore Modeling, Molecular Docking, Molecular Dynamics, and In-Vitro Cytotoxicity Studies. J. Mol. Struct. 1224. 129289.
Downloads
Additional Files
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Jurnal Sains dan Kesehatan
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
