Novel Compounds Design of Acertannin, Hamamelitannin, and Petunidin-3-Glucoside Typical Compounds of African Leaves (Vernonia amygdalina Del) as Antibacterial Based on QSAR and Molecular Docking

Ilham Kurniawan (1), Laksmi Ambarsari (2), Popi Asri Kurniatin (3), Setyanto Tri Wahyudi (4)
(1) Department of Biochemistry, Faculty of Mathematics and Natural Sciences, IPB University, Bogor, Indonesia, Indonesia,
(2) Department of Biochemistry, Faculty of Mathematics and Natural Sciences, IPB University, Bogor, Indonesia, Indonesia,
(3) Department of Biochemistry, Faculty of Mathematics and Natural Sciences, IPB University, Bogor, Indonesia, Indonesia,
(4) Department of Physics, Faculty of Mathematics and Natural Sciences; Tropical Biopharmaca Research Center, IPB University, Bogor, Indonesia, Indonesia

Abstract

Antibacterial secondary metabolites such as tannins and their derivatives are found in the Vernonia amygdalina Del. Antibiotic resistance can develop due to overuse, reducing the efficacy of drugs to prevent and treat infections. This research aims to use the Quantitative Structure-Activity Relationship (QSAR) and the semi-empirical method Austin Model 1 (AM1) to design a modified novel compound from African leaves that has improved antibacterial activity. This research includes a descriptor calculation of QSAR using AM1 MOE on typical compounds from African leaves, and calculation results are chosen based on a multilinear regression statistical analysis. The model equation represents the three primary parameters of QSAR, which are electronic, hydrophobic, and steric parameters, which will be used to measure modified compounds. Molecular docking using Autodock Tools (The Scripps Research Institute, USA), and analysis of results of docking Autodock Tools using Discovery Studio 3.5 Client. The best QSAR model obtained is LogEC50 = (0.829 x LogP) - (1,302 x AM1_HOMO) - (0.339 x AM1_dipole) - (5,128 x mr) + (0.145 x vol) - (11,355). The results showed that EC50 prediction of modified hamamelitannin has the best activity with the lowest ΔGbind -9.0 kcal/mol and inhibition constant of 0.249 μM. In summary, the novel compound's design calculation has better antibacterial activity, as indicated by a lower EC50, than fosfomycin or compounds without modification. The modified hamamelitannin compound was found to have better antibacterial activity (prediction EC50 = 0.1933 μM) than the original (experimental EC50 = 145.50 μM).

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References

Adeniji, S. E., Uba, S., & Uzairu, A. (2018). QSAR Modeling and Molecular Docking Analysis of Some Active Compounds against Mycobacterium tuberculosis Receptor (Mtb CYP121). Journal of Pathogens, 2018, 1–24. https://doi.org/10.1155/2018/1018694

Ananto, A. D. (2019). Analisis QSAR senyawa turunan meisoindigo sebagai antikanker payudara. AMINA (Ar-Raniry Chemistry Journal), 1(1), 1–5. https://doi.org/10.22373/amina.v1i1.7

Ananto, A. D., Muliasari, H., & Hadisaputra, S. (2020). Design New Compound of Meisoindigo Derivative as Anti Breast Cancer Based on QSAR Approach. Jurnal Kimia Sains Dan Aplikasi, 23(9), 305–311. https://doi.org/10.14710/jksa.23.9.305-311

Baber, J. C., Thompson, D. C., Cross, J. B., & Humblet, C. (2009). GARD: A generally applicable replacement for RMSD. Journal of Chemical Information and Modeling, 49(8), 1889–1900. https://doi.org/10.1021/ci9001074

Barreteau, H., Kovač, A., Boniface, A., Sova, M., Gobec, S., & Blanot, D. (2008). Cytoplasmic steps of peptidoglycan biosynthesis. In FEMS Microbiology Reviews (Vol. 32, Issue 2, pp. 168–207). FEMS Microbiol Rev. https://doi.org/10.1111/j.1574-6976.2008.00104.x

Basant, N., Gupta, S., & Singh, K. P. (2015). Predicting Toxicities of Diverse Chemical Pesticides in Multiple Avian Species Using Tree-Based QSAR Approaches for Regulatory Purposes. Journal of Chemical Information and Modeling, 55(7), 1337–1348. https://doi.org/10.1021/acs.jcim.5b00139

Demchuk, E., Ruiz, P., Chou, S., & Fowler, B. A. (2011). SAR/QSAR methods in public health practice. In Toxicology and Applied Pharmacology (Vol. 254, Issue 2, pp. 192–197). Academic Press. https://doi.org/10.1016/j.taap.2010.10.017

Dermawan, D., Sumirtanurdin, R., & Dewantisari, D. (2019). Molecular Dynamics Simulation Estrogen Receptor Alpha againts Andrographolide as Anti Breast Cancer. Indonesian Journal of Pharmaceutical Science and Technology, 6(2), 65. https://doi.org/10.24198/ijpst.v6i2.18168

Du, W., Brown, J. R., Sylvester, D. R., Huang, J., Chalker, A. F., So, C. Y., Holmes, D. J., Payne, D. J., & Wallis, N. G. (2000). Two active forms of UDP-N-acetylglucosamine enolpyruvyl transferase in gram-positive bacteria. Journal of Bacteriology, 182(15), 4146–4152. https://doi.org/10.1128/JB.182.15.4146-4152.2000

Eschenburg, S., Priestman, M. A., Abdul-Latif, F. A., Delachaume, C., Fassy, F., & Schönbrunn, E. (2005). A novel inhibitor that suspends the induced fit mechanism of UDP-N-acetylglucosamine enolpyruvyl transferase (MurA). Journal of Biological Chemistry, 280(14), 14070–14075. https://doi.org/10.1074/jbc.M414412200

Farha, A. K., Yang, Q. Q., Kim, G., Li, H. Bin, Zhu, F., Liu, H. Y., Gan, R. Y., & Corke, H. (2021). Tannins as an alternative to antibiotics. Food Bioscience, 38(10), 1–11. https://doi.org/10.1016/j.fbio.2020.100751

Han, H., Yang, Y., Olesen, S. H., Becker, A., Betzi, S., & Schönbrunn, E. (2010). The fungal product terreic acid is a covalent inhibitor of the bacterial cell wall biosynthetic enzyme UDP-N-acetylglucosamine 1-carboxyvinyltransferase (MurA). Biochemistry, 49(19), 4276–4282. https://doi.org/10.1021/bi100365b

Kalaria, P. N., Satasia, S. P., & Raval, D. K. (2014). L-Proline promoted green and regioselective synthesis of a novel pyrazole based trifluoromethylated fused thiazolopyran scaffold and its biological evaluation. RSC Advances, 4(61), 32353–32362. https://doi.org/10.1039/c4ra04283b

Kementerian Kesehatan Republik Indonesia. (2011). Pedoman Umum Penggunaan Antibiotik. In Departemen Kesehatan Republik Indonesia.

Khan, T., Dixit, S., Ahmad, R., Raza, S., Azad, I., Joshi, S., & Khan, A. R. (2017). Molecular docking, PASS analysis, bioactivity score prediction, synthesis, characterization and biological activity evaluation of a functionalized 2-butanone thiosemicarbazone ligand and its complexes. Journal of Chemical Biology, 10(3), 91–104. https://doi.org/10.1007/S12154-017-0167-Y

Kong, M., & Ryu, S. (2015). Bacteriophage PBC1 and its endolysin as an antimicrobial agent against Bacillus cereus. Applied and Environmental Microbiology, 81(7), 2274–2283. https://doi.org/10.1128/AEM.03485-14

Kurniawan, I. (2021). Analisis Penambatan Molekuler Turunan Senyawa Tanin Daun Afrika (Vernonia amygdalina Del) terhadap MurA sebagai Antibakteri. http://repository.ipb.ac.id/handle/123456789/107056

Kurniawan, I., & Zahra, H. (2021). Review: Gallotannins; Biosynthesis, Structure Activity Relationship, Anti-inflammatory and Antibacterial Activity. Current Biochemistry, 8(1), 1–16. https://doi.org/10.29244/cb.8.1.1

Kwon, S., Bae, H., Jo, J., & Yoon, S. (2019). Comprehensive ensemble in QSAR prediction for drug discovery. BMC Bioinformatics, 20(1), 1–12. https://doi.org/10.1186/s12859-019-3135-4

Li, S., Xiong, Q., Lai, X., Li, X., Wan, M., Zhang, J., Yan, Y., Cao, M., Lu, L., Guan, J., Zhang, D., & Lin, Y. (2016). Molecular Modification of Polysaccharides and Resulting Bioactivities. Comprehensive Reviews in Food Science and Food Safety, 15(2), 237–250. https://doi.org/10.1111/1541-4337.12161

Ma’rufah, S. H., & Aziz, S. A. (2019). Respon Pertumbuhan Setek Batang Daun Afrika (Vernonia amygdalina) dengan Penggunaan Bagian Batang dan Media Tanam. Buletin Agrohorti, 7(1), 53–61. https://doi.org/10.29244/AGROB.V7I1.24408

Madigan, M. M., Bender, K. S., Buckley, D. H., Sattley, W. M., & Stahl, D. A. (2016). Brock Biology of Microorganisms. Fifteenth Global Edition. In S. Beauparlant (Ed.), Pearson. Pearson education Lmtd.

Mao, J., Li, T., Zhang, N., Wang, S., Li, Y., Peng, Y., Liu, H., Yang, G., Yan, Y., Jiang, L., Liu, Y., Li, J., & Huang, X. (2021). Dose Optimization of Combined Linezolid and Fosfomycin against Enterococcus by Using an In Vitro Pharmacokinetic/Pharmacodynamic Model. Microbiology Spectrum, 9(3). https://doi.org/10.1128/spectrum.00871-21

Naven, R. T., & Louise-May, S. (2015). Computational toxicology: Its essential role in reducing drug attrition. Human and Experimental Toxicology, 34(12), 1304–1309. https://doi.org/10.1177/0960327115605440

Oko, O. J., Odoh, R., Tongu, S. M., Anidobu, C. O., Udegbunam, I. S., & Umar, H. (2018). Alkaloid, tannin profiles and mineral element composition of the leaves and stem of Vernonia amygdalina (bitter leaf) plant harvested from Wukari town, Taraba state, North-East Nigeria. European Journal of Pure and Applied Chemistry, 5(2). www.idpublications.org

Pratiwi, R. D., & Gunawan, E. (2018). Uji Aktivitas Antibakteri Ekstrak Etanol Daun Afrika (Vernonia amygdalina Delile) Asal Papua Terhadap Bakteri Staphylococcus aureus Dan Escherichia coli. PHARMACY: Jurnal Farmasi Indonesia (Pharmaceutical Journal of Indonesia), 15(2), 148–157. https://doi.org/10.30595/PHARMACY.V15I2.3493

Richter, K., Van Den Driessche, F., & Coenye, T. (2017). Innovative approaches to treat Staphylococcus aureus biofilm-related infections. In Essays in Biochemistry (Vol. 61, Issue 1, pp. 61–70). Essays Biochem. https://doi.org/10.1042/EBC20160056

Skarzynski, T., Mistry, A., Wonacott, A., Hutchinson, S. E., Kelly, V. A., & Duncan, K. (1996). Structure of UDP-N-acetylglucosamine enolpyruvyl transferase, an enzyme essential for the synthesis of bacterial peptidoglycan, complexed with substrate UDP-N-acetylglucosamine and the drug fosfomycin. Structure, 4(12), 1465–1474. https://doi.org/10.1016/S0969-2126(96)00153-0

Wang, T. Y., Li, Q., & Bi, K. S. (2018). Bioactive flavonoids in medicinal plants: Structure, activity and biological fate. In Asian Journal of Pharmaceutical Sciences (Vol. 13, Issue 1, pp. 12–23). Elsevier. https://doi.org/10.1016/j.ajps.2017.08.004

Watanabe, M., & Devkota, H. P. (2017). Antioxidant Phenolic Constituents from the Leaves of Acer ginnala var aidzuense. Journal of Natural Remedies, 17(1), 9–12. https://doi.org/10.18311/JNR/2017/15632

Yeni, Y., Supandi, S., & Khalishah, Y. (2018). HKSA dan Penambatan Molekuler Senyawa Turunan Kumarin sebagai Anti Kanker Kolon. BIOEDUSCIENCE: Jurnal Pendidikan Biologi Dan Sains, 2(1), 45. https://doi.org/10.29405/j.bes/2145-521355

Authors

Ilham Kurniawan
Laksmi Ambarsari
Popi Asri Kurniatin
Setyanto Tri Wahyudi
stwahyudi@apps.ipb.ac.id (Primary Contact)
Kurniawan, I. ., Ambarsari, L. ., Kurniatin, P. A. ., & Wahyudi, S. T. . (2023). Novel Compounds Design of Acertannin, Hamamelitannin, and Petunidin-3-Glucoside Typical Compounds of African Leaves (Vernonia amygdalina Del) as Antibacterial Based on QSAR and Molecular Docking. Jurnal Jamu Indonesia, 8(2), 29–38. https://doi.org/10.29244/jji.v8i2.326

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