ANTIBACTERIAL ACTIVITY OF AKAR KUNING (ARCANGELISIA FLAVA) SECONDARY METABOLITES: MOLECULAR DOCKING APPROACH
Objectives: Akar kuning (Arcangelisia flava) was known to have various pharmacological activities including as antibacterial. Several Gram-positive and Gram-negative bacteria show response to akar kuning secondary metabolites, although the type of metabolites that inhibit the growth of each type of bacteria not yet known. This study aims to obtain the prediction of metabolites from akar kuning with the greatest antibacterial potential against various types of antibacterial receptors.
Methods: Molecular docking was performed using Autodock Vina 1.1.2 on several secondary metabolites of akar kuning against active site of several antibacterial receptors that were known for many antibiotics including as cell wall, protein, nucleic acid synthesis inhibitors, and antimetabolites. The main parameter used was the free energy of binding as affinity marker.
Results: The docking results show that among 11 metabolites studied, 6-hydroxyfibraurin, berberine, and fibleucin provided the lowest free energy of binding between 11 antibacterial receptors compared with natural substrates or inhibitors from each receptor. Interesting results show by berberine as inhibitor of protein synthesis with possibility of allosteric site discovery. Berberine also shows more than 75% similarity with natural substrate of cell wall inhibition receptor, indicating possible similar type of interaction.
Conclusion: Overall, it seems that for the selected secondary metabolites of akar kuning, the main mechanism of action was the inhibition of protein and cell wall synthesis, which was shown by berberine.
2. Kong C, Eng S, Lim M, Nathan S. Beyond traditional antimicrobials: A Caenorhabditis elegans model for discovery of novel anti-infectives. Front Microbiol 2016;7:1956.
3. Ma W, Kahn RE, Richt JA. The pig as a mixing vessel for influenza viruses: Human and veterinary implications. J Mol Genet Med 2009;3:158-66.
4. Smith JR. Oseltamivir in human avian influenza infection. J Antimicrob Chemother 2010;65 Suppl 2:ii25-33.
5. Yap PS, Yiap BC, Ping HC, Lim SH. Essential oils, a new horizon in combating bacterial antibiotic resistance. Open Microbiol J 2014;8:6 14.
6. Munita JM, Arias CA. Mechanisms of antibiotic resistance. Microbiol Spectr 2016;4:10.
7. Pratama MR, Gusdinar T. Between artemisinin and derivatives with neuraminidase: A docking study insight. Asian J Pharm Clin Res 2017;10:304-8.
8. Atanasov AG, Waltenberger B, Pferschy-Wenzig E, Linder T, Wawrosch C, Uhrin P, et al. Discovery and resupply of pharmacologically active plant-derived natural products: A review. Biotechnol Adv 2015;33:1582-614.
9. Pratama MR, Sutomo S. Chemical structure optimization of lupeol as ER-A and HER2 inhibitor. Asian J Pharm Clin Res 2018;11:298-303.
10. Cragg GM, Newman DJ. Natural products: A continuing source of novel drug leads. Biochim Biophys Acta 2013;1830:3670-95.
11. Pratama MR. Akar kuning (Arcangelisia flava) as neuraminidase inhibitor: Molecular docking and pharmacophore optimization approach. Adv Health Sci Res 2017;6:502-11.
12. Ginovyan M, Petrosyan M, Trchounian A. Antimicrobial activity of some plant materials used in Armenian traditional medicine. BMC Complement Altern Med 2017;17:50.
13. Yi F, Li L, Xu L, Meng H, Dong Y, Liu H, et al. In silico approach in reveal traditional medicine plants pharmacological material basis. Chin Med 2018;13:33.
14. Setyowati R, Sudarsono S, Setyowati EP. The effect of water soluble stem extract kayu kuning (Arcangelisia flava L Merr) on the growth inhibition of Candida albicans ATCC 10231 and Trichophyton mentagrophytes in vitro. Biol Med Natl Prod Chem 2014;3:15-9.
15. Pratama MR. Akar kuning (Arcangelisia flava) as EGFR inhibitor: In silico study. J Farmagazine 2016;3:6-16.
16. Rosita M, Monalisa SS, Rozik M. In vitro test of natural antibacterial activity of yellow-fruit moonseed Arcangelisia flava Merr. Leaf on bacterium Pseudomonas fluorescens under different doses. AACL Bioflux 2018;11:288-94.
17. Heryani H, Nugroho A. Study of yellow root (Arcangelisia flava Merr) as a natural food additive with antimicrobial and acidity-stabilizing effects in the production process of palm sugar. Procedia Environ Sci 2015;23:346-50.
18. Alves MJ, Froufe HJ, Costa AF, Santos AF, Oliveira LG, Osorio SR, et al. Docking studies in target proteins involved in antibacterial action mechanisms: Extending the knowledge on standard antibiotics to antimicrobial mushroom compounds. Molecules 2014;19:1672-84.
19. Dharani RS, Ranjitha R, Sripathi R, Muhammad KS, Ravi S. Docking studies in target proteins involved in antibacterial action mechanisms: Alkaloids isolated from Scutellaria genus. Asian J Pharm Clin Res 2016;9:121-5.
20. Cheng K, Zheng QZ, Qian Y, Shi L, Zhao J, Zhu HL, et al. Synthesis, antibacterial activities and molecular docking studies of peptide and schiff bases as targeted antibiotics. Bioorg Med Chem 2009;17:7861 71.
21. Oâ€™Boyle NM, Banck M, James CA, Morley C, Vandermeersch T, Hutchison GR, et al. Open babel: An open chemical toolbox. J Cheminform 2011;3:33.
22. Adawiyah R, Suryani S, Artika IM. Histone acetyltransferase P300/CBP-associated factor inhibition by quercetin as anticancer drug candidate with in silico and in vitro approach. Int J Pharm Pharm Sci 2016;8:211-5.
23. Trott O, Olson AJ. Autodock vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. J Comput Chem 2010;31:455-61.
24. Forli S. Charting a path to success in virtual screening. Molecules 2015;20:18732-58.
25. Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, et al. AutoDock4 and autoDockTools4: Automated docking with selective receptor flexibility. J Comput Chem 2009;30:2785-91.
26. Pratama MR, Pratomo GS. Pharmacophore optimization of berberine as HER2 inhibitor. J Pharm Indones 2017;14:109-17.
27. Du X, Li Y, Xia YL, Ai SM, Liang J, Sang P, et al. Insights into protein-ligand interactions: Mechanisms, model, and methods. Int J Mol Sci 2016;17:144.
28. Meng XY, Zhang HX, Mezei M, Cui M. Molecular docking: A powerful approach for structure-based drug discovery. Curr Comput Aided Drug Des 2011;7:146-57.
29. Chen J, Almo SC, Wu Y. General principles of binding between cell surface receptors and multi-specific ligands: A computational study. PLoS Comput Biol 2017;13:e1005805.
30. Malmstrom RD, Watowich SJ. Using free energy of binding calculations to improve the accuracy of virtual screening predictions. J Chem Inf Model 2011;51:1648-55.
31. Ramirez D, Caballero J. Is it reliable to use common molecular docking methods for comparing the binding affinities of enantiomer pairs for their protein target? Int J Mol Sci 2016;17:pii E525.
32. Purwanggana A, Mumpuni E, Mulatsari E. In vitro and in silico antibacterial activity of 1.5-bis (3â€™-ethoxy-4â€™-hydroxyphenyl)-1-4-pentadiene-3-one. Int J Pharm Pharm Sci 2018;10:70-6.
33. Pagadala NS, Syed K, Tuszynski J. Software for molecular docking: A review. Biophys Rev 2017;9:91-102.
34. Feng R, Qu J, Zhou W, Wei Q, Yin Z, Du Y, et al. Antibacterial activity and mechanism of berberine on avian Pasteurella multocida. Int J Clin Exp Med 2016;9:22866-92.
35. Peng L, Kang S, Yin Z, Jia R, Song X, Li L, et al. Antibacterial activity and mechanism of berberine against Streptococcus agalactiae. Int J Clin Exp Pathol 2015;8:5217-23.
36. Watt IN, Montgomery MG, Runswick MJ, Leslie AG, Walker JE. Bioenergetic cost of making an adenosine triphosphate molecule in animal mitochondria. Proc Natl Acad Sci 2010;107:16823-7.
37. Rittie L, Perbal B. Enzymes used in molecular biology: A useful guide. J Cell Commun Signal 2008;2:25-45.
38. Silhavy TJ, Kahne D, Walker S. The bacterial cell envelope. Cold Spring Harb Perspect Biol 2010;2:a000414.
39. Nurhayati B, Wibowo MS, Widyastuti Y, Erawijantari PP, Widowati W, Pratama MR, et al. In silico analysis of plantaricin EF that expressed by plasmid-associated bacteriocin production gene of Lactobacillus plantarum IBL-2 for anti-candida agent potential. Res J Microbiol 2015;10:582-91.
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.