INHIBITION OF CYCLOOXYGENASE-2 USING BIOACTIVE COMPOUND DERIVED MORINGA OLEIFERA THROUGH MOLECULAR DOCKING APPROACH
Abstract
ABSTRAKRespon tubuh terhadap iritasi, radiasi, infeksi, dan cedera menyebabkan peradangan. Penelitian ini menggunakan pendekatan molecular docking untuk mengeksplorasi potensi senyawa bioaktif dari Moringa oleifera terhadap reseptor COX-2. Penelitian diawali dengan redocking untuk validasi metode. Sepuluh senyawa bioaktif diperoleh dari https://pubchem.ncbi.nlm.nih.gov dan reseptor COX-2 dari www.rcsb.com. Senyawa dari Moringa oleifera dianalisis menggunakan Lipinski's Rule of File dan properti ADMET. Energi pengikatan dan interaksi residu asam amino dihitung menggunakan Autodock Tools 1.5.6 dengan memanfaatkan Lamarckian Genetic Algorithm (LGA). Hasil perhitungan menunjukkan delapan senyawa bioaktif yang memenuhi Lipinski's Rule of Five. Benzil glukosinolat memiliki energi pengikatan yang lebih rendah daripada ligan asalnya, yaitu -8,06 kJ mol-1 dengan residu asam amino TYR385, SER530, TYR355, HIS90, ARG513, LEU352, dan GLN192. Studi ini menunjukkan bahwa benzil glukosinolat, senyawa yang diisolasi dari Moringa oleifera, menunjukkan potensi yang menjanjikan sebagai penghambat enzim COX-2. Analisis komputasional menunjukkan bahwa molekul yang terjadi secara alami ini kemungkinan memiliki sifat antiinflamasi yang signifikan dengan menargetkan jalur siklooksigenase-2 secara selektif. Penelitian ini memberikan dasar yang kuat untuk riset masa depan di bidang penemuan dan perancangan obat, khususnya dalam pencarian agen antiinflamasi alami. Metodologi dan hasil yang disajikan di sini dapat menjadi referensi berharga bagi para peneliti yang mengeksplorasi fitokimia lain, sebagai petunjuk potensial untuk mengembangkan terapi antiinflamasi yang lebih aman dan lebih efektif.
Kata kunci: antiinflamasi, COX-2, docking molekuler, Moringa oleifera
ABSTRACT
The body's response to irritation, radiation, infection, and injury causes inflammation. This research used a molecular docking approach to explore the potential of bioactive compounds from Moringa oleifera against the COX-2 receptor. It was initiated with redocking for method validation. Ten bioactive compounds were obtained from https://pubchem.ncbi.nlm.nih.gov and COX-2 receptors from www.rcsb.com, respectively. The compounds from Moringa oleifera were analyzed using Lipinski's Rule of File and ADMET properties. The binding energy and amino acid residue interaction were calculated using Autodock Tools 1.5.6 utilizing the Lamarckian Genetic Algorithm (LGA). The calculation results showed eight bioactive compounds that fulfill Lipinski's Rule of Five. Benzyl glucosinolate has a lower binding energy than the native ligand, namely -8.06 kJ mol-1with amino acid residues TYR385, SER530, TYR355, HIS90, ARG513, LEU352, and GLN192. This study demonstrates that benzyl glucosinolate, a compound isolated from Moringa oleifera, exhibits promising potential as a COX-2 enzyme inhibitor. The computational analysis suggests that this naturally occurring molecule may possess significant anti-inflammatory properties by selectively targeting the cyclooxygenase-2 pathway. Furthermore, this research provides a solid foundation for future investigations in the field of drug discovery and design, particularly in the pursuit of natural anti-inflammatory agents. The methodology and results presented here can serve as a valuable reference for researchers exploring other phytochemicals as potential leads for developing safer and more effective anti-inflammatory therapeutics.
Keywords: anti-inflammation, COX-2, molecular docking, Moringa oleifera
Downloads
Download data is not yet available.
References
Allouche, A. R. (2011). Gabedit—A graphical user interface for computational chemistry softwares. Journal of computational chemistry, 32(1), 174-182.
Cáceres, E. L., Tudor, M., & Cheng, A. C. (2020). Deep learning approaches in predicting ADMET properties. Future Medicinal Chemistry, 12(22), 1995-1999.
Chen, L., Deng, H., Cui, H., Fang, J., Zuo, Z., Deng, J., ... & Zhao, L. (2018). Inflammatory responses and inflammation-associated diseases in organs. Oncotarget, 9(6), 7204.
Deng, M., Jin, C., & Mao, X. (2023). Approximating knapsack and partition via dense subset sums. In Proceedings of the 2023 Annual ACM-SIAM Symposium on Discrete Algorithms (SODA) (pp. 2961-2979). Society for Industrial and Applied Mathematics.
Ehigiator, B., Loveth Iyanyi, U., Mobisson, K. S., & Ukata, O. (2023). In vivo and in silico investigation of effects of ethanol extract of moringa oleifera leaves on female fertility, using fruit flies and molecular docking. Journal of Clinical and Basic Research, 7(3), 1-6.
Emelda, E., Nugraeni, R., & Damayanti, K. (2023). Eksplorasi Tanaman Herbal Indonesia sebagai Anti Inflamasi. INPHARNMED Journal (Indonesian Pharmacy and Natural Medicine Journal), 6(2), 58-64.
Hamdy, N. M. (2024). Exploring the anti-inflammatory potential of the polyphenolic compounds in Moringa oleifera leaf: in silico molecular docking. Egyptian Journal of Basic and Applied Sciences, 11(1), 367-385.
Hartanti, I. R., Putri, A. A., Auliya, A. S., Triadenda, A. L., Laelasari, E., Suhandi, C., & Muchtaridi, M. (2022). Molecular docking senyawa xanton, benzofenon, dan triterpenoid sebagai antidiabetes dari ekstrak tumbuhan garcinia cowa. Jurnal Kimia, 16(1), 72-83.
Haugland, S. W. (2021). The changing notion of chimera states, a critical review. Journal of Physics: Complexity, 2(3), 032001.
Karami, T. K., Hailu, S., Feng, S., Graham, R., & Gukasyan, H. J. (2022). Eyes on Lipinski's rule of five: A New “rule of thumb” for physicochemical design space of ophthalmic drugs. Journal of ocular pharmacology and therapeutics, 38(1), 43-55.
Neelaveni, K., RajendraPrasad, Y., Krishna, K., & Lavanya, J. (2024). Indole moiety bearing Pyrimidine-2-thiolderivatives: Synthesis, Characterization and their insilico molecular docking studies in comparison to standard ligand drug.
Marchi, S., Guilbaud, E., Tait, S. W., Yamazaki, T., & Galluzzi, L. (2023). Mitochondrial control of inflammation. Nature Reviews Immunology, 23(3), 159-173.
Marek-Jozefowicz, L., Nedoszytko, B., Grochocka, M., Żmijewski, M. A., Czajkowski, R., Cubała, W. J., & Slominski, A. T. (2023). Molecular mechanisms of neurogenic inflammation of the skin. International Journal of Molecular Sciences, 24(5), 5001.
Mumtaz, M. Z., Kausar, F., Hassan, M., Javaid, S., & Malik, A. (2021). Anticancer activities of phenolic compounds from Moringa oleifera leaves: in vitro and in silico mechanistic study. Beni-Suef University Journal of Basic and Applied Sciences, 10, 1-11.
Nunes, C. D. R., Barreto Arantes, M., Menezes de Faria Pereira, S., Leandro da Cruz, L., de Souza Passos, M., Pereira de Moraes, L., ... & Barros de Oliveira, D. (2020). Plants as sources of anti-inflammatory agents. Molecules, 25(16), 3726.
Orlando, B. J., & Malkowski, M. G. (2016). Substrate-selective inhibition of cyclooxygeanse-2 by fenamic acid derivatives is dependent on peroxide tone. Journal of Biological Chemistry, 291(29), 15069-15081.
Pitaloka, A. D., Nurhijriah, C. Y., Kalina, K., Musyaffa, H. A., & Azzahra, A. M. (2023). Penambatan Molekuler Konstituen Kimia Tumbuhan Bawang Dayak (Eleutherine palmifolia (L.) Merr) terhadap Reseptor VHR sebagai Kandidat Obat Antikanker Serviks. Indonesian Journal of Biological Pharmacy, 3(2), 83-95.
Sahu, V. K., Singh, R. K., & Singh, P. P. (2022). Extended rule of five and prediction of biological activity of peptidic HIV-1-PR inhibitors. Universal Journal of Pharmacy and Pharmacology, 20-42.
Sanzeni, A., Akitake, B., Goldbach, H. C., Leedy, C. E., Brunel, N., & Histed, M. H. (2020). Inhibition stabilization is a widespread property of cortical networks. Elife, 9, e54875.
Sohail, R., Mathew, M., Patel, K. K., Reddy, S. A., Haider, Z., Naria, M., ... & Razzaq, W. (2023). Effects of non-steroidal anti-inflammatory drugs (NSAIDs) and gastroprotective NSAIDs on the gastrointestinal tract: a narrative review. Cureus, 15(4).
Truong, J., George, A., & Holien, J. K. (2021). Analysis of physicochemical properties of protein–protein interaction modulators suggests stronger alignment with the “rule of five”. RSC Medicinal Chemistry, 12(10), 1731-1749.
Utami, W., Aziz, H. A., Fitriani, I. N., Zikri, A. T., Mayasri, A., & Nasrudin, D. (2020, June). In silico anti-inflammatory activity evaluation of some bioactive compound from ficus religiosa through molecular docking approach. In Journal of Physics: Conference Series (Vol. 1563, No. 1, p. 012024). IOP Publishing.
Venkatraman, V. (2021). FP-ADMET: a compendium of fingerprint-based ADMET prediction models. Journal of cheminformatics, 13, 1-12.
Wei, Y., Li, S., Li, Z., Wan, Z., & Lin, J. (2022). Interpretable-ADMET: a web service for ADMET prediction and optimization based on deep neural representation. Bioinformatics, 38(10), 2863-2871.
Wiyono, A. S., & Diyah, N. W. (2023). Molecular docking of 5-o-benzoylpinostrobin derivatives from Boesenbergia pandurata roxb. as anti-inflammatory. Journal of Public Health in Africa, 14(Suppl 1).
Wulan, H., Widagdo, D. P., & Aulia, C. (2021). Potensi Ekstrak Etanol Daun Kelor sebagai Antiinflamasi, Penetapan Kadar Flavanoid Total. Media Farmasi Indonesia, 16(2), 1693-1697.
Xu, Y. B., Chen, G. L., & Guo, M. Q. (2019). Antioxidant and anti-inflammatory activities of the crude extracts of Moringa oleifera from Kenya and their correlations with flavonoids. Antioxidants, 8(8), 296.
Zakiyah, W., Wibowo, S. P. S., Elyyana, N., Darmawan, S. A. N., Lestari, S. A., Sa'diyyah, N., ... & Mulki, M. A. (2022). Literature Review: Study of molecular mechanism level of NSAID class of drugs as COX-2 inhibitors. Jurnal EduHealth, 13(02), 572-580.
Cáceres, E. L., Tudor, M., & Cheng, A. C. (2020). Deep learning approaches in predicting ADMET properties. Future Medicinal Chemistry, 12(22), 1995-1999.
Chen, L., Deng, H., Cui, H., Fang, J., Zuo, Z., Deng, J., ... & Zhao, L. (2018). Inflammatory responses and inflammation-associated diseases in organs. Oncotarget, 9(6), 7204.
Deng, M., Jin, C., & Mao, X. (2023). Approximating knapsack and partition via dense subset sums. In Proceedings of the 2023 Annual ACM-SIAM Symposium on Discrete Algorithms (SODA) (pp. 2961-2979). Society for Industrial and Applied Mathematics.
Ehigiator, B., Loveth Iyanyi, U., Mobisson, K. S., & Ukata, O. (2023). In vivo and in silico investigation of effects of ethanol extract of moringa oleifera leaves on female fertility, using fruit flies and molecular docking. Journal of Clinical and Basic Research, 7(3), 1-6.
Emelda, E., Nugraeni, R., & Damayanti, K. (2023). Eksplorasi Tanaman Herbal Indonesia sebagai Anti Inflamasi. INPHARNMED Journal (Indonesian Pharmacy and Natural Medicine Journal), 6(2), 58-64.
Hamdy, N. M. (2024). Exploring the anti-inflammatory potential of the polyphenolic compounds in Moringa oleifera leaf: in silico molecular docking. Egyptian Journal of Basic and Applied Sciences, 11(1), 367-385.
Hartanti, I. R., Putri, A. A., Auliya, A. S., Triadenda, A. L., Laelasari, E., Suhandi, C., & Muchtaridi, M. (2022). Molecular docking senyawa xanton, benzofenon, dan triterpenoid sebagai antidiabetes dari ekstrak tumbuhan garcinia cowa. Jurnal Kimia, 16(1), 72-83.
Haugland, S. W. (2021). The changing notion of chimera states, a critical review. Journal of Physics: Complexity, 2(3), 032001.
Karami, T. K., Hailu, S., Feng, S., Graham, R., & Gukasyan, H. J. (2022). Eyes on Lipinski's rule of five: A New “rule of thumb” for physicochemical design space of ophthalmic drugs. Journal of ocular pharmacology and therapeutics, 38(1), 43-55.
Neelaveni, K., RajendraPrasad, Y., Krishna, K., & Lavanya, J. (2024). Indole moiety bearing Pyrimidine-2-thiolderivatives: Synthesis, Characterization and their insilico molecular docking studies in comparison to standard ligand drug.
Marchi, S., Guilbaud, E., Tait, S. W., Yamazaki, T., & Galluzzi, L. (2023). Mitochondrial control of inflammation. Nature Reviews Immunology, 23(3), 159-173.
Marek-Jozefowicz, L., Nedoszytko, B., Grochocka, M., Żmijewski, M. A., Czajkowski, R., Cubała, W. J., & Slominski, A. T. (2023). Molecular mechanisms of neurogenic inflammation of the skin. International Journal of Molecular Sciences, 24(5), 5001.
Mumtaz, M. Z., Kausar, F., Hassan, M., Javaid, S., & Malik, A. (2021). Anticancer activities of phenolic compounds from Moringa oleifera leaves: in vitro and in silico mechanistic study. Beni-Suef University Journal of Basic and Applied Sciences, 10, 1-11.
Nunes, C. D. R., Barreto Arantes, M., Menezes de Faria Pereira, S., Leandro da Cruz, L., de Souza Passos, M., Pereira de Moraes, L., ... & Barros de Oliveira, D. (2020). Plants as sources of anti-inflammatory agents. Molecules, 25(16), 3726.
Orlando, B. J., & Malkowski, M. G. (2016). Substrate-selective inhibition of cyclooxygeanse-2 by fenamic acid derivatives is dependent on peroxide tone. Journal of Biological Chemistry, 291(29), 15069-15081.
Pitaloka, A. D., Nurhijriah, C. Y., Kalina, K., Musyaffa, H. A., & Azzahra, A. M. (2023). Penambatan Molekuler Konstituen Kimia Tumbuhan Bawang Dayak (Eleutherine palmifolia (L.) Merr) terhadap Reseptor VHR sebagai Kandidat Obat Antikanker Serviks. Indonesian Journal of Biological Pharmacy, 3(2), 83-95.
Sahu, V. K., Singh, R. K., & Singh, P. P. (2022). Extended rule of five and prediction of biological activity of peptidic HIV-1-PR inhibitors. Universal Journal of Pharmacy and Pharmacology, 20-42.
Sanzeni, A., Akitake, B., Goldbach, H. C., Leedy, C. E., Brunel, N., & Histed, M. H. (2020). Inhibition stabilization is a widespread property of cortical networks. Elife, 9, e54875.
Sohail, R., Mathew, M., Patel, K. K., Reddy, S. A., Haider, Z., Naria, M., ... & Razzaq, W. (2023). Effects of non-steroidal anti-inflammatory drugs (NSAIDs) and gastroprotective NSAIDs on the gastrointestinal tract: a narrative review. Cureus, 15(4).
Truong, J., George, A., & Holien, J. K. (2021). Analysis of physicochemical properties of protein–protein interaction modulators suggests stronger alignment with the “rule of five”. RSC Medicinal Chemistry, 12(10), 1731-1749.
Utami, W., Aziz, H. A., Fitriani, I. N., Zikri, A. T., Mayasri, A., & Nasrudin, D. (2020, June). In silico anti-inflammatory activity evaluation of some bioactive compound from ficus religiosa through molecular docking approach. In Journal of Physics: Conference Series (Vol. 1563, No. 1, p. 012024). IOP Publishing.
Venkatraman, V. (2021). FP-ADMET: a compendium of fingerprint-based ADMET prediction models. Journal of cheminformatics, 13, 1-12.
Wei, Y., Li, S., Li, Z., Wan, Z., & Lin, J. (2022). Interpretable-ADMET: a web service for ADMET prediction and optimization based on deep neural representation. Bioinformatics, 38(10), 2863-2871.
Wiyono, A. S., & Diyah, N. W. (2023). Molecular docking of 5-o-benzoylpinostrobin derivatives from Boesenbergia pandurata roxb. as anti-inflammatory. Journal of Public Health in Africa, 14(Suppl 1).
Wulan, H., Widagdo, D. P., & Aulia, C. (2021). Potensi Ekstrak Etanol Daun Kelor sebagai Antiinflamasi, Penetapan Kadar Flavanoid Total. Media Farmasi Indonesia, 16(2), 1693-1697.
Xu, Y. B., Chen, G. L., & Guo, M. Q. (2019). Antioxidant and anti-inflammatory activities of the crude extracts of Moringa oleifera from Kenya and their correlations with flavonoids. Antioxidants, 8(8), 296.
Zakiyah, W., Wibowo, S. P. S., Elyyana, N., Darmawan, S. A. N., Lestari, S. A., Sa'diyyah, N., ... & Mulki, M. A. (2022). Literature Review: Study of molecular mechanism level of NSAID class of drugs as COX-2 inhibitors. Jurnal EduHealth, 13(02), 572-580.
Published
2024-09-04
How to Cite
ANTARI, L. et al.
INHIBITION OF CYCLOOXYGENASE-2 USING BIOACTIVE COMPOUND DERIVED MORINGA OLEIFERA THROUGH MOLECULAR DOCKING APPROACH.
Jurnal Kimia (Journal of Chemistry), [S.l.], p. 177-185, sep. 2024.
ISSN 2599-2740.
Available at: <https://ojs.unud.ac.id/index.php/jchem/article/view/116649>. Date accessed: 21 nov. 2024.
Issue
Section
Articles
This work is licensed under a Creative Commons Attribution 4.0 International License
