Synthesis of Chalcone Derivative Compounds from 4 Chloro Acetophenone and In Silico Activity Test as Candidate Antidiabetic Compounds
DOI:
https://doi.org/10.37859/jp.v15i1.7829
Keywords:
Chalcone, Stirring, Antidiabetic, Alpha glucosidase, in silico
Abstract
This study aimed to synthesize the chalcone derivative (E)-1-(4-chlorophenyl)-3-(3-hydroxyphenyl)prop-2-en-1-one (CX) under alkaline conditions using a magnetic stirrer. 4-Chloroacetophenone was reacted with 3-hydroxybenzaldehyde in ethanol (p.a.) as the solvent, with 60% KOH as the base catalyst. The product was purified by recrystallization using ethanol (p.a.), yielding 72.67%. The purity of the synthesized compound was evaluated using thin-layer chromatography (TLC) and melting point measurements. The compound was subsequently evaluated for its potential antidiabetic activity through in silico studies. Molecular docking was performed to predict the interactions between the compounds and the protein (PDB ID: 1GFY). The results showed that the cDOCKER energy of the reference COL ligand was more favorable than that of CX. The COL ligand exhibited a cDOCKER energy of -49.4051 kcal/mol and formed four hydrogen bonds with the key amino acid residues Gly220, Arg221, Ser216, and Asp181. In comparison, the synthesized CX compound exhibited a cDOCKER energy of -29.293 kcal/mol and formed three hydrogen bonds with the key amino acid residues Ser216, Asp181, and Lys120. These findings suggest that CX may have potential as a candidate compound for antidiabetic drug development.
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References
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Wang, H., & Zeng, J., 2009. Iodine-Catalyzed Efficient Synthesis of Chalcones by Grinding Under Solvent-Free Conditions. Canadian Journal of Chemistry, 87(9), 1209‒1212.
Xue, K., Sun, G., Zhang, Y., Chen, X., Zhou, Y., Hou, J., Long, H., Zhang, Z., Lei, M., & Wu, W., 2021. A New Method for the Synthesis of Chalcone Derivatives Promoted by Pph3/I2under Non-Alkaline Conditions. Synthetic Communications, 51(4), 625‒634.
Syahri, J., Hilma, R., Ali, A.H., Ismail, N., Ling, N.Y., Nurlaili., Nurohmah, B.A., Agustar, H.K., Ling, L.Y & Latip, J. 2023. Chalcone Mannich base derivatives: synthesis, antimalarial activities against Plasmodium knowlesi, and molecular docking analysis. Royal Society of Chemistry, 13, 36035–36047.
Xu D., Tsai C.J. & Nussinov R. (1997). Hydrogen bonds and salt bridges across protein-protein interfaces. Protein engineering, 10(9), 999–101.
Lelita, R., Gunawan, R., & Astuti, W. 2017. Molecuar Docking Studies Quercetin, Chalcone, and Its Derivate Inhibot to Breast Cancer Cells MCF-7 (Michigan Cancer Foundation-7). Jurnal Atomik., 01 (2) hal 190-196.
Murtiningsih, M. K., Pandelaki, K., & Sedli, B. P. (2021). Gaya Hidup sebagai Faktor Risiko Diabetes Melitus Tipe 2. E-CliniC, 9(2), 328- 333.
P. Patel & A. Macerollo, “Diabetes mellitus: Diagnosis and screening,” Am. Fam. Physician, vol. 81, no. 7, pp. 863–870, 2010.
D. M. Nathan, “Diabetes: Advances in diagnosis and treatment,” JAMA - J. Am. Med. Assoc., vol. 314, no. 10, pp. 1052–1062, 2015.
International Diabetes Federation the IDF Diabetes Atlas, 2017.
Fathurohman, I., & Fadhilah, M. 2016. Gambaran Tingkat Risiko dan Faktor-Faktor yang Berhubungan dengan Risiko Diabetes Mellitus Tipe 2. Jurnal Kedokteran Yarsi. 24 (3) : 186-202.
Prabawati, S.Y., Khusnuryani, A., & Khamidinal. 2017. Sintesis Senyawa Kalkon Bebas Pelarut Sebagai Zat Antibakteri. Jurnal Alchemy, 13 (1) : 95-102.
Dias, T. A., Duarte, C. L., Lima, C. F., Proença, M. F., & Pereira-Wilson, C., 2013. Superior Anticancer Activity of Halogenated Chalcones and Flavonols Over the Natural Flavonol Quercetin. European Journal of Medicinal Chemistry, 65, 500‒510.
M. R. Jayapal & N. Y. Sreedhar, “Anhydrous K2CO3 as catalyst for the synthesis of chalcones under Microwave Irradiation,” J. Pharm. Sci. Res., vol. 2, no. 10, pp. 644–647, 2010.
Sang, Z., Song, Q., Cao, Z., Deng, Y., Tan, Z., & Zhang, L., 2021. Design, Synthesis and Evaluation of Novel Dimethylamino Chalcone-O-Alkylamines Derivatives as Potential Multifunctional Agents Against Alzheimer's Disease. European Journal of Medicinal Chemistry, 216, 113310.
Fijriani, R,. 2019. Variasi waktu penggerusan pada sintesis senyawa turunan kalkon dari vanillin dan asetofenon. Skripsi. Universitas Islam Negeri Maulana Malik Ibrahim. Malang.
Dona R., Furi M., Frimayanti N., Zamri A., & Nahdiah N. Studi In Silico dan Pengaruh Gugus Metoksi pada Hasil Sintesis Analog Kalkon terhadap Inhibisi Enzim α-glukosidase. Jurnal Sains Farmasi & Klinis, 2022, 9 (1) : 12–23.
Rahman, M.A. 2011. Chalcone : A Valuable Insight into the Recent Advances and Potential Pharmacological Activities. Chemical Sciences Journal. Volume 2011 : CSJ-29.
Konduru, N. K., Dey, S., Sajid, M., Owais, M., & Ahmed, N., 2013. Synthesis and Antibacterial and Antifungal Evaluation of Some Chalcone Based Sulfones and Bisulfones. European Journal of Medicinal Chemistry, 59, 23‒30.
Park, S., Kim, E. H., Kim, J., Kim, S. H., & Kim, I., 2018. Biological Evaluation of Indolizine-Chalcone Hybrids as New Anticancer Agents. European Journal of Medicinal Chemistry, 144, 435‒443.
Rashid, H. U., Xu, Y., Ahmad, N., Muhammad, Y., & Wang, L., 2019. Promising Anti-Inflammatory Effects of Chalcones via Inhibition of Cyclooxygenase, Prostaglandin E(2), Inducible NO Synthase and Nuclear Factor κb Activities. Bioorganic Chemistry, 87, 335‒365.
Castaño, L. F., Cuartas, V., Bernal, A., Insuasty, A., Guzman, J., Vidal, O., Rubio, V., Puerto, G., Lukáč, P., Vimberg, V., Balíková-Novtoná, G., Vannucci, L., Janata, J., Quiroga, J., Abonia, R., Nogueras, M., Cobo, J., & Insuasty, B., 2019. New Chalcone-Sulfonamide Hybrids Exhibiting Anticancer and Antituberculosis Activity. European Journal of Medicinal Chemistry, 176, 50‒60.
Hu, Y., Hu, C., Pan, G., Yu, C., Ansari, M. F., Yadav Bheemanaboina, R. R., Cheng, Y., Zhou, C., & Zhang, J., 2021. Novel Chalcone-Conjugated, Multi-Flexible End-Group Coumarin Thiazole Hybrids as Potential Antibacterial Repressors Against Methicillin-Resistant Staphylococcus Aureus. European Journal of Medicinal Chemistry, 222, 113628.
Nurlaili., Jasril., & Teruna H.Y. Uji Aktivitas Antioksidan Senyawa Pirazolin 3-(2- Metoksi-Fenil)-5-Naftalen-1-Il-4,5-Dihidro-1h-Pirazol. Jurnal Photon, 2018, 8 (2) : 53-58.
Nafillah, K., & Anwar, C. 2023. Karakterisasi dan Studi Sinergi Analog Kurkumin dari Senyawa 4-Metoksibenzaldehida sebagai Antidiabetes dengan Metode Iodin. Indonesian Journal of Pure and Applied Chemistry. 6 (3) : 101-113.
Y. Eryanti, A. Zamri, J. Jasril, & R. Rahmita, “Sintesis Turunan 2’-hidroksi Kalkon melalui Kondensasi Claisen-Schmidt dan Uji Aktivitasnya sebagai Antimikroba,” J. Natur Indones., vol. 12, no. 2, p. 223, 2012.
Wayan, S,. 2016. Sintesis senyawa kalkon serta uji aktivitas sebagai antioksidan. Jurnal Kimia. 10 (1) : 75-80.
Kakkar S, Kumar S, Lim SM, Ramasamy K, Mani V, Shah SAA, Narasimhan B (2018) Design, synthesis and biological evaluation of 3-(2-aminooxazol-5-yl)-2H-chromen-2-one derivatives. Chem Cent J. 12(130):1–13.
Syahri,J., Hilma, R., Nurlaili,. Saputri, H., Nasution, S.Z., & Nurohmah, B.A. 2023. Synthesis, Characterization, Biological Evaluation, and Docking Simulation of Chalcone Derivatives as Potent Antibacterial Agents. AIP Conference Proceeding. 2601, 020044-1–020044-7.
Calvino, V., Picallo, M., López-Peinado, A. J., Martín-Aranda, R. M., & Durán-Valle, C. J., 2006. Ultrasound Accelerated Claisen–Schmidt Condensation: a Green Route to Chalcones. Applied Surface Science, 252 (17), 6071‒6074.
Ahmad, M. R., Girija Sastry, V., Bano, N., & Anwar, S., 2016. Synthesis of Novel Chalcone Derivatives by Conventional and Microwave Irradiation Methods and Their Pharmacological Activities. Arabian Journal of Chemistry, 9, S931‒S935.
Wang, H., & Zeng, J., 2009. Iodine-Catalyzed Efficient Synthesis of Chalcones by Grinding Under Solvent-Free Conditions. Canadian Journal of Chemistry, 87(9), 1209‒1212.
Xue, K., Sun, G., Zhang, Y., Chen, X., Zhou, Y., Hou, J., Long, H., Zhang, Z., Lei, M., & Wu, W., 2021. A New Method for the Synthesis of Chalcone Derivatives Promoted by Pph3/I2under Non-Alkaline Conditions. Synthetic Communications, 51(4), 625‒634.
Syahri, J., Hilma, R., Ali, A.H., Ismail, N., Ling, N.Y., Nurlaili., Nurohmah, B.A., Agustar, H.K., Ling, L.Y & Latip, J. 2023. Chalcone Mannich base derivatives: synthesis, antimalarial activities against Plasmodium knowlesi, and molecular docking analysis. Royal Society of Chemistry, 13, 36035–36047.
Xu D., Tsai C.J. & Nussinov R. (1997). Hydrogen bonds and salt bridges across protein-protein interfaces. Protein engineering, 10(9), 999–101.
Lelita, R., Gunawan, R., & Astuti, W. 2017. Molecuar Docking Studies Quercetin, Chalcone, and Its Derivate Inhibot to Breast Cancer Cells MCF-7 (Michigan Cancer Foundation-7). Jurnal Atomik., 01 (2) hal 190-196.
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Published
2024-11-30
How to Cite
nasution, N., Jannah, M., & Syahri, J. (2024). Synthesis of Chalcone Derivative Compounds from 4 Chloro Acetophenone and In Silico Activity Test as Candidate Antidiabetic Compounds. Photon: Jurnal Sain Dan Kesehatan, 15(1), 10–18. https://doi.org/10.37859/jp.v15i1.7829
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