Synthesis of a Cinnamic Acid Derivative and Bioactivity as an Anticancer Based on Result Quantitative Structure Activity Relationship (QSAR) Analysis
DOI:
https://doi.org/10.20956/ica.v13i1.9565Keywords:
QSAR, caffeic acid, phenethylaminoAbstract
Synthesis of compound (E)-4-(3-oxo-3-(phenethylamino)prop-1-en-1-il)-1,2-phenylene diacetate (3) analogue (E)-3-(3,4-dihydroxyphenyl)-N-phenethylacrylamide as a recommendation from the QSAR analysis was carried out. The synthesis of these compounds uses the starting material of caffeic acid through the stages of the reaction of acetylation, chlorination, and amidation. Acetylation was carried out using acetic anhydride in pyridine at room temperature for 4 hours. Chlorination was carried out using thionyl chloride reagent in dimethylphromamide solvent under reflux conditions at 80ºC for 4 hours, followed by amidation using phenethylamine in dichloromethane solvent at room temperature for 1 hour. The structure of each phase of the reaction product is identified using FT-IR spectroscopy. Acetylation produces white crystalline solids with melting point 182-184oC, and amidation produces compound 3 in the form of white crystals with melting point 170-173oC. The results of activity tests on murine leukaemia P-388 cells showed that the activity of compound 3 was classified as very strong (IC50 = 0,5 µg /mL) so that it was potentially used as an anticancer drug.
References
Abdel-Hameed E.-S.S., Bazaid S.A., Shohayeb M.M., El-Sayed M.M. dan El-Walkil E.A., 2012, Phytochemical Studies and Evaluation of Antioxidant, Anticancer and Antimicrobial Properties of Conocarpus erectus L. Growing in Taif, Saudi Arabia, Eur. J. of Medicinal Plants, 2 (2), 93–112.
Firdaus, Soekamto, N. H., Permatasari, N. U., Seniwati, Sukarti, dan Makmun. 2012. Synthesis of Secondary and Tertiary Derivatives of p-Kumaramide and Its Activity Test as Antitumor P-388 Leukemia Cells. Indonesia Chimica Acta. 5 (2): 10-16.
Firdaus, N H Soekamto, Seniwati, M F Islam dan Sultan. 2016. Phenethyl ester and amide of Ferulic Acids: Synthesis and bioactivity against P-388 Leukemia Murine Cells. J. Phys.: Conf. Ser. 979 012016
Cho, M. S., 2014. Caffeic acid phenethyl ester promotes antiinflammatory effects by inhibiting MAPK and NF-κB signaling in activated HMC-1 human mast cells. Pharm Biol, 2014; 52(7): 926–932
Hung, C.C., Tsai, W.J., , Kuo, L.M.Y., and Kuo, Y.H. 2005. Evaluation of Caffeic Acid Amide Analogues as Anti-platelet Aggregation and Anti-oxidative Agents. Bioorganic & Medicinal Chemistry. 13: 1791–1797 Nakamura, K., Nakajima, T., Aoyama, T., dan Okitsu, S., 2014, One-pot Esterification and Amidation of Phenolic Acids, Tetrahedron, 30: 1-11.
Nakamura, K. 2014. One-pot esterification and amidation of phenolic acids. Tetrahedron, 1 – 11
Peng, W., Wu, J.G., Jian, Y.B., Liu, Y.J., Sun, T., et al. 2015. Antitumor Activity of 4-O-(2”-O-acetyl-6”-O-p-coumaroyl-β-D-glucopyranosyl)-p-coumaric Acid Against Lung Cancers Via Mitochondrial-mediated Apoptosis, Chemico-Biological Interactions. 233: 8-13.
Pranowo, H.D., 2003, Computational Chemistry, Center for Computational Chemistry Indonesia-Austria Kimia, FMIPA UGM, Yogyakarta
Rajan, P., Vedernikova, I., Cos, P., Berghe, D. V., Augustynsa, K., dan Haemers, K., 2001, Synthesis and Evaluation of Caffeic Acid Amides as Antioxidants, Bioorg. Med. Chem. Lett., 11: 215-217.
Sharma, P. 2011. Cinnamic acid derivatives: A new chapter of various pharmacological activities. Journal of Chemical and Pharmaceutical Research. 3 (2): 403-423.
Simon-Hettich, Rothfuss, A., Thomas, S., H., 2006, Use of Computer-assisted Prediction of Toxic Efffects of Chemical Substances, Toxicology 224, 154-162.
Stankova, I. and Spasova, M. 2009. Hydroxycinnamic Acid Amides with Oxazole-Containing Amino Acid: Synthesis and Antioxidant Activity. Z. Naturforsch. 64 (c): 176-178.
Tropsha, A., Golbraikh, A., 2007, Predictive QSAR Modelling Workflow, Model Applicability Domains, and Virtual Screening. Current Pharmaceutical Design, 13, 3494-3504
Zhang, P., Yuping Tang, Nian-Guang Li, Yue Zhu, and Jin-Ao Duan. 2014. Bioactivity and Chemical Synthesis of Caffeic Acid Phenethy Ester and Its Derivatives. Molecules. 19: 16458-16476.
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