SIMULASI DOCKING SENYAWA AKTIF DAUN BINAHONG SEBAGAI INHIBITOR ENZYME ALDOSE REDUCTASE

Andrio Suhadi; Rizarullah Rizarullah; Feriyani Feriyani

doi:10.22435/sel.v6i2.1651

Andrio Suhadi
Rizarullah Rizarullah
Feriyani Feriyani

DOI: https://doi.org/10.22435/sel.v6i2.1651

Keywords: binahong leaves, molecular docking, zopolrestat. oleonolic acid , ursolic acid

Abstract

Sindroma metabolik merupakan masalah dunia yang disebabkan salah satunya oleh diabetes mellitus. Daun binahong merupakan tanaman yang sering digunakan untuk mengobati berbagai penyakit. Penelitian ini bertujuan untuk melihat aktivitas inhibisi senyawa daun binahong untuk menghambat aldose reductase yang berperan mengubah glukosa menjadi sorbitol dengan cara simulasi docking. Senyawa dari daun binahong adalah asam ursolat, vitexin dan oleonalat (ligan uji). Senyawa tersebut di ambil melalui situs pubchem, sedangkan enzyme aldose reductase (reseptor) didapat dari bank protein dunia dengan kode PDB 2HV5. Penelitian ini menggunakan teknik In Sillico dengan menggunakan perangkat lunak AutoDock Vina dan Discovery Studio serta Ligplot sebagai visualisasinya. Hasil optimasi gridbox dengan melakukan penambatan ulang ligan pembanding dan diperoleh RMSD sebesar 0,7 Å. Hasil docking menunjukkan energi bebas gibbs (∆G) Aldose Reductase (-11,7), Vitexin (-8,3), Asam Ursolat (-7,7) dan Oleonalat (-8,6) yang menunjukan adanya reaksi inhibisi yang stabil dari senyawa daun binahong dan ligan pembanding. Berdasarkan aturan dari Lipinski’s Rule menunjukan senyawa dari daun binahong memenuhi dari aturan Lipinski’s Rule yang berarti dapat digunakan secara oral kecuali Vitexin dan ligan pembanding zopolrestat melebihi dari jumlah atom.

The metabolic syndrome is the cause of death around the world caused by diabetic mellitus. Binahong leaf is a kind of plant that is widely used to treat various diseases. This study aims to investigate the inhibitory activity of binahong leaves compound in inhibiting the aldose reductase which has role of converting glucose into sorbitol by docking simulation. The compound of binahong leaves consists of ursolic acid, vitexin, and oleonolic acid (ligand testing). These compound were taken from PubChem site, while aldose reductase enzyme (receptor) was obtained from the world protein bank with PDB 2HV5 code. This study incorporated in silica technique by using Auto dock vina software, Discovery Studio and Ligplot as visualization. The result of grid box optimization by redocking comparative ligand was 0.7Å RMSD. The docking result showed that the free Gibbs energy (∆G) of aldose reductase was (-11.7), Vitexin (-8.3), Ursolic acid (-7.7) and Oleonolic acid (-8.6). These value suggested that there was a stable inhibition reaction from the binahong leaves compound and the comparative ligand. Based on the Lipinski Rule, the composition of binahong leaves compound meets the Lipinski Rule criteria which means this medicine can be used orally except for vitexin and comparative ligands of zopolrestate which exceed the number of the atom.

References

1. Al-Nakeeb Y, Lyons M, Collins P, Al-Nuaim A, et al. Obesity, Physical Activity and Sedentary Behavior Amongst Britisht and Saudi Youth: a cross-cultural study. Int J Environ Reseacrh Public Heal. 2012.
2. Rizzo A, Goldberg T, Silva C, Kurokawa C, Nunes H. Metabolic Syndrome Risk Factors In Overweight, Obese, and Extremely Obese Brazilian Adolescents. Nutr J. 2013.
3. Ranasinghe P, Mathangasinghe Y, Jayawardena R, Hills AP, Misra A. Prevalence and trends of metabolic syndrome among adults in the asia-pacific region : a systematic review. BMC Public Health. 2017:1-9. doi:10.1186/s12889-017-4041-1.
4. Ansarimoghaddam A, Ali H, Iraj Z, Sohrab I, Ali H. Diabetes & Metabolic Syndrome : Clinical Research & Reviews Prevalence of metabolic syndrome in Middle-East countries : Meta-analysis of cross-sectional studies. Diabetes Metab Syndr Clin Res Rev. 2017. doi:10.1016/j.dsx.2017.11.004.
5. Diabetes DOF. Diagnosis and Classification of Diabetes Mellitus. Am Diabetes Assoc. 2013;36:67-74. doi:10.2337/dc13-S067.
6. Chawla A, Chawla R, Jaggi S. Microvascular and Macrovascular Complications In Diabetes Mellitus: Distinct or Continuum. Indian J Endocr Metab. 2016;20(4). doi:10.4103/2230-8210.183480.
7. KEMENKES RI. Situasi Gangguan Penglihatan Dan Kebutaan. Jakarta; 2013.
8. Selawa W, Runtuwene MRJ, Citraningtyas G. Kandungan flavonoid dan kapasitas antioksidan total ekstrak etanol daun binahong [Anredera cordifolia(Ten.)Steenis.]. Pharmacon J Ilm Farm - UNSRAT. 2013;2(1):18-23.
9. Baxevanis. Bioinformatics a Practical Guide to The Analysis of Genes and Proteins Second Edition. 2nd ed. Wiley-Interscience; 2001.
10. Bosco K, Brasseur R. The Ramachandran Plots of Glycine and Pre-Proline. BMC STRUCT BIOl. 2005;5(14). doi:10.1186/1472-6807-5-14.
11. FKUI DF. Farmakologi Dan Terapi. 6th ed. Jakarta; 2013.
12. Rachmania RA, Supandi, Larasati OA. Analisis In-Silico Senyawa Diterpenoid Lakton Herba Sambiloto (Andrographis Paniculata Ness) Pada Reseptor Alpha-Glucosidase Sebagai Anti Diabetes Tipe II. Pharm J Indones. 2015;12(2).
13. A.Lipinski C. Lead and Drug Like Compounds : The Rule Of Five Revolution. Drug Discov. 2004. doi:0.1016/j.ddtec.2004.11.007.
14. Setiawan T. Studi molecular docking ekstrak kurkuminoid asal wonogiri sebagai inhibitor enzim dna topoisomerase ii. 2015.
15. Choy Y Bin, Prausnitz MR. The Rule of Five for Non-Oral Routes of Drug Delivery: Ophthalmic, Inhalation and Transdermal. 2011. doi:10.1007/s11095-010-0292-6.
16. Mardianingrum R, Herlina T, Supratman U. Isolasi dan Molecular Docking Senyawa 6,7- Dihidro-17 Hidroksierisotrin Dari Daun Dadap Belendung (Erythrina Poeppigian) Terhadap Aktivitas Sitotoksik Antikanker Payudara MCF-7. Chim er Nat Acta. 2013;3(3). doi:10.24198/cna.v3.n3.9213.
17. Kartasasmita RE, Herowati R, Harmastuti N, Gusdinar T. Querectin Derivatives Docking Based On Study of Flavonoids Interaction to Cyclooxygenase -2 Docking Turunan Kuersetin Berdasarkan Studi Interaksi Flavonoid Terhadap Enzim. IndoJ.chem. 2010;9(2):297-302.
18. Lee EH, Popov SA, Lee JY, et al. Inhibitiory Effect of Ursolic Acid Dericaties o Recombinant Human Aldose Reductase. Russ J Bioorganic Chem. 2011;37(69). doi:10.1134/S1068162011050050.
19. Díez-Dacal, Sánchez-Gómez, Sánchez-Murcia, et al. Molecular Interactions and Implication of Aldose Reductase Inhibition by PGA1 and clinically used prostaglandins. Mol Phamacol. 2016;89(1):42-52. doi:10.1124/mol.115.100693.