SINTESIS ANALOG KURKUMIN MONOKETON BERBAHAN DASAR SINAMALDEHIDA  DAN UJI AKTIVITASNYA SEBAGAI INHIBITOR  ENZIM α-GLUKOSIDASE

Yunia Mardianis; Chairil Anwar; Winarto Haryadi

doi:10.21831/jsd.v6i2.15831

SINTESIS ANALOG KURKUMIN MONOKETON BERBAHAN DASAR SINAMALDEHIDA DAN UJI AKTIVITASNYA SEBAGAI INHIBITOR ENZIM α-GLUKOSIDASE

Yunia Mardianis, Department of Chemistry, Faculty of Mathmatics and Natural Sciences,Gadjah Mada University, Indonesia
Chairil Anwar, Department of Chemistry, Faculty of Mathmatics and Natural Sciences,Gadjah Mada University, Indonesia
Winarto Haryadi, Department of Chemistry, Faculty of Mathmatics and Natural Sciences,Gadjah Mada University, Indonesia

10.21831/jsd.v6i2.15831

Abstract

Telah dilakukan sintesis analog kurkumin monoketon sebagai senyawa target yang berbahan dasar sinamaldehida dan uji aktivitasnya sebagai inhibitor enzim α-glukosidase. Tahap sintesis melibatkan reaksi kondensasi aldol silang Claisen-Schmidt dengan variasi keton sehingga dihasilkan senyawa analog kurkumin monoketon. Pengujian aktivitas antidiabetes senyawa analog kurkumin dilakukan melalui inhibisi enzim α-glukosidase yang diisolasi dari beras lapuk (Oryza sativa). Tahapan awal penelitian ini yaitu analog kurkumin (2E,5E)-2,5-bis((E)-3-fenilalilidin) siklopentanon disintesis dengan mereaksikan sinamaldehid dan monoketon siklopentanon dalam pelarut etanol. Sintesis tersebut dilakukan dalam kondisi basa KOH dengan pengadukan pada suhu 52 °C selama 50 menit. Senyawa hasil sintesis dianalisis strukturnya menggunakan FTIR, direct inlet-MS, ¹H- dan ¹³C-NMR. Tahap selanjutnya analog kurkumin hasil sintesis diuji aktivitasnya sebagai inhibitor enzim α-glukosidase. Hasil penelitian menunjukkan bahwa analog kurkumin monoketon hasil sintesis diperoleh rendemen sebesar 72,15%. Hasil berupa padatan berwana kuning dengan titik leleh sebesar 196,20–200,10 °C. Hasil uji inhibisi terhadap enzim α-glukosidase mengindikasi bahwa analog kurkumin memiliki aktivitas antidiabetik dan cukup berpotensi untuk menginhibisi enzim α-glukosidase dengan persentase inhibisi sebesar 70,71%.

THE SYNTHESIS OF CURCUMINE ANALOGUE MONOCETONE FROM CINAMALDEHYDE AND ITS ACTIVITY TEST AS α-GLUCOCYDE ENZYME INHIBITOR

The synthesis of curcumin analog monoketone as target compounds from cinnamaldehyde and inhibition assay against α-glucosidase enzyme had been performed. The stepwise of synthesis was performed by aldol condensation Claisen-Schmidt reaction and used ketone to give curcumin analog monoketone. The antidiabetic activity of curcumin analog was carried out by inhibition test against α-glucosidase enzyme isolated from rotten (Oryza sativa). The first step of synthesis (2E,5E)-2,5-bis((E)-3-phenylallylidene) cyclopentanone was started by reacting cinnamaldehyde and cyclopentanone as monoketone in etanol as solvent. The synthesis was carried out in base condition (KOH) by stirring at 52 °C for 50 minutes. The structures of product was identified by using FTIR, direct inlet-MS, ¹H- and ¹³C-NMR. Futhermore, the activity of curcumin analog was tested against with α-glucosidase enzyme inhibition. The results show that the curcumin analog was yielded in 72.15% as yellow solid. The melting point of curcumin analog was at 196.20–200.10 °C. The inhibition against α-glucosidase enzyme indicated that the curcumin analog was potential to inhibit α-glucosidase enzyme with the highest activity by giving inhibtion percentage of about 70.71% at 2.5 mM.

Keywords

analog kurkumin monoketon, sinamaldehida, α-glukosidase, antidiabetik

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References

Wells, G.B., Dipiro, J.T., Schwinghammer, T.L., and Dipiro, C.V., 2009, Pharmacotheraphy Handbook, 7^th Edition, McGraw-Hill Companies, Inc., New York

Guo, L.P., Jiang, T.F., Lv, Z.H., and Wang, Y.H., 2010, Screening α-Glucosidase Inhibitors from Traditional Chinese Drugs by Capillary Electrophoresis with Electrophoretically Mediated Microanalysis, J. Pham. Biomed. Anal., 53, 1250–1253

Lam, S., Chen, J., Kang, C., and Lee, S., (2008), α-Glucosidase Inhibitors from The Seeds of Syagrus romanzoffiana, J. Phytochem., 69, 1173–1178

Mayfield, J., 1998, Diagnosis and Classification of Diabetes Mellitus: New Cretria, Am. Fam. Physician, 58, 1355–1362

Herfindal, E.T. and Gourley, D.R., 2000, Textbook of Therapeutics, Drug, and Disease Management, 7^th edition, Baltimore, Maryland, 377–406

Shinde, J., Taldone, T., Barlette, M., Kunaparaju, N., Bo, H., and Kumar, S., 2008, α-Glucosidase Inhibitory Acrtivity of Syzygium cumini, Skeels Seed Karnel In Vitro and in Goto-Kakizaki (GK) Rats, J. Chem. Educ., 343, 1278–1281

Nampoothiri, S.V., Prathapan, A., Cherian L. O., Raghu, K.G.,Venugovalan, V.V., and Sundaresan, A, 2011, In Vitro Antioxidant and Inhibitory Potential of Terminalia bellerica and Emblica officinalis Fruits Against Oxidation and Enzymes Linked to Type 2 Diabetes, Food Chem. Toxicol., 49, 125-131

Ren, S., Duoduo, X., Zhi, P., Yang, G., Zhenguo, J., and Qipin, G., 2011, Two Flavonone Compounds from Litchi (Litchi chinensis Sonn), Seeds, One Previously Unreported, and Apparsial of Their α-Glucosidase Inhibitory Activities, Food Chem., 127, 1760–1763

Lee, S.L., Huang, W.J., Lin, W.W., Lee, S.S., and Chen, C.H., 2005, Preparation and Anti-Inflammatory Activities of Diarylheptanoid and Diarylheptylamine Analogs, Bioorg. Med. Chem., 13, 1643–1675

Babu, P.S., Prabuseenivasan, S., and Ignacimuthu, S., 2007, Cinnamaldehyde—A potential antidiabetic agent, J. Phytomed., 14 (1), 15–22

Allen, R. W., Schwartzman, E., Baker, W. L., Coleman, C. I., and Phung, O. J., 2013, Cinnamon Use in Type 2 Diabetes: An Updated Systematic Review and Meta-Analysis. Ann. Fam. Med., 11 (5), 452–459

Lekshmi, P.C., Arimboor, R., Indulekha, P.S., and Menon, A.N., 2012, Turmeric (Curcuma longa L.) Volatile Oil Inhibits Key Enzymes Linked to Type 2 Diabetes, J. Food Sci. Nutr., 63 (7), 832-834

Eryanti, Y., Narulita, Y., Hendra, R., Yuharmen, Syahri, J., and Zamri, A., 2011, Synthesizing Derivatives from Cyclopentanone Analogue Curcumin and Their Toxic, Antioxidant, and Anti-Inflammatory Activities, Makara Sains, 15 (2), 117-123

Yuan, X., Li, H., Bai, H., Su, Z., Xiang, Q., Wang, C., Zhao, B., Zhang, Q., Chu, Y., and Huang, Y., 2014, Synthesis of Novel Curcumin Analogues for Inhibition of 11β-Hydroxysteroid Dehydrogenase Type 1 with Anti-Diabetic Properties, Eur. J. Med. Chem., 77, 223-230

Bruice, P.Y., 2007, Organic Chemistry, 5^th edition, New York.

Pavia, D.L., Lampman, G.M., and Kriz, G.S., 2001. Introduction to Spectroscopy, Brooks/Cole Thomson Learning, New York

Supratman, U., 2010, Elusidasi Struktur Senyawa Organik, Widya Padjadjaran, Bandung

Du, Z., Liu R.,Shao, W., Mao, X., Ma, L., Gu, L., Huang, Z., and Chan, A.S.C., 2006, α-Glucosidase Inhibition of Natural Curcuminoids and Curcumin Analogs, Eur. J. Med. Chem., 41(2), 213-218

[19] Kumar, S., Narwal, S., Kumar, V., and Prakash, O., 2011, α-Glucosidase Inhibitors from Plants: A Natural Approach to Treat Diabets. Pharmacol. Rev., 20

[20] Vessal, M., Hemati, M., and Vasei, M., 2003, Antidiabetic Effect of Quercetin in Streptozin Induced Diabetic Rats, Comp. Biochem. Physycol. C. Toxicol. Pharmacol., 135, 357-364

[21] Annapurna, H.V., Apoorva, B., Ravichandran, N., Arun K.P., Brindha, P., and Swaminathan, S., 2013, Isolation and in Silico Evaluation of Antidibetic Molecules of Cynodon dactylon (L.), J. Mol. Graph Modell, 39, 87-97

DOI: https://doi.org/10.21831/jsd.v6i2.15831