Molecular docking of 5-o-benzoylpinostrobin derivatives from <em>Boesenbergia pandurata</em> roxb. as anti-inflammatory

Authors

  • Anang Setyo Wiyono Doctoral Program of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya; Diploma III Study Program of Pharmaceutical and Food Analysis, Faculty of Pharmacy, Institut Ilmu Kesehatan Bhakti Wiyata, Kediri
  • Siswandono Siswandono Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya
  • Nuzul Wahyuning Diyah Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya

DOI:

https://doi.org/10.4081/jphia.2023.2532

Keywords:

Docking, Benzoylpinostrobin, Cyclooxygenase-2, Anti-inflammatory.

Abstract

Background: The use of NSAIDs, also known as non-steroidal anti-inflammatory drugs, has numerous adverse effects and consequences. For this reason, it is necessary to develop rational drugs as safer anti-inflammatory drugs with fewer side effects. Temu Kunci rhizome contains Pinostrobin (5-hydroxy-7- methoxyflavanone), which is believed to have anti-inflammatory properties.

Objective: This study aims to determine the strongest anti-inflammatory activity at the cyclooxygenase-2 (COX-2) receptor through the 5-O-Benzoylpinostrobin derivative design. Methods: AutoDockTools on the COX-2 receptor (PDB code: 5IKR) were used in molecular docking in this study. The metrics employed were binding afinity (ΔG), inhibition constant (Ki), which serve as indicators of affinities, and amino acid residue similarity, which serves as a measure of the similarity of interactions. Predictive scores were confirmed by Molecular Docking Simulation.

Results: The top five 5-O-Benzoylpinostrobin derivatives show a high affinity for the COX-2 receptor compared to Pinostrobin as a marker compound of Boesenbergia pandurata Roxb and furthermore give the lowest inhibition constant (Ki) and the highest negative binding free energy (ΔG), 35.40, 45.21, 54.75, 64.43, 76.97 nM and -10.16, -10.02, -9.91, -9.81, -9.7 kcal/mol. Interestingly, the five 5-O-Benzoylpinostrobin derivatives also have higher affinity than the native ligand Mefenamic acid, which is known to be a non-selective COX-2 inhibitor. The highest predicted affinity was shown by 4-Nitro-5-O-benzoylpinostrobin for the COX-2 receptor (PDP ID: 5IKR), with a higher predicted affinity for Mefenamic acid.

Conclusion: The five selected 5-O-Benzoylpinostrobin derivatives were potent modifications of pinostrobin as an anti-inflammatory because they showed a higher affinity than Pinostrobin and Mefenamic acid. This study demonstrated that it is highly feasible to produce and test the novel 5-O-Benzoylpinostrobin derivative in vivo, specifically 4-Nitro-5-O-benzoylpinostrobin.

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References

Bindu S, Mazumder S, Bandyopadhyay U. Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective. Biochem Pharmacol. (Internet) 2020;180:114147. DOI: https://doi.org/10.1016/j.bcp.2020.114147

Mehuys E, Crombez G, Paemeleire K, et al. Self-Medication With Over-the-Counter Analgesics: A Survey of Patient Characteristics and Concerns About Pain Medication. J Pain. (Internet) 2019;20:215-23. DOI: https://doi.org/10.1016/j.jpain.2018.09.003

Wheatley BM, Nappo KE, Christensen DL, et al. Effect of NSAIDs on Bone Healing Rates: A Meta-analysis. J Am Acad Orthop Surg. (Internet) 2019;27:e330-6. DOI: https://doi.org/10.5435/JAAOS-D-17-00727

Idacahyati K, Nofianti T, Aswa GA, Nurfatwa M. Hubungan Tingkat Kejadian Efek Samping Antiinflamasi Non Steroid dengan Usia dan Jenis Kelamin, Jurnal Farmasi Dan Ilmu Kefarmasian Indonesia. (Internet) 2019;6:56-61. DOI: https://doi.org/10.20473/jfiki.v6i22019.56-61

Levita J, Nawawi A, Mutholib A, Ibrahim S. Andrographolide inhibits COX-2 expression in human fibroblast cells due to its interaction with arginine and histidine in cyclooxygenase site. J Applied Sci 2010;10:1481-4. DOI: https://doi.org/10.3923/jas.2010.1481.1484

Lin N, Liu C, Xiao C, et al. Triptolide, a diterpenoid triepoxide, suppresses inflammation and cartilage destruction in collagen-induced arthritis mice. Biochem Pharmacol 2007;73:136-46. DOI: https://doi.org/10.1016/j.bcp.2006.08.027

González Y, Torres-Mendoza D, Jones GE, Fernandez PL. Marine Diterpenoids as Potential Anti-Inflammatory Agents. Mediators Inflamm 2015;2015:263543. DOI: https://doi.org/10.1155/2015/263543

Atun S, Handayani S. Fitokimia Tumbuhan Temukunci (Boesenbergia Rotunda): Isolasi, Identifikasi Struktur, Aktivitas Biologi, dan Sintesis Produk Nanopartikelnya. Yogyakarta: Penerbit K-Media 2017.

Siswandono, Widyowati R, Suryadi A, et al. Molecular Modeling, Synthesis, And QSAR of 5-O-Acylpinostrobin Derivatives as Promising Analgesic Agent. RASAYAN J Chem 2020;13:2559-68. DOI: https://doi.org/10.31788/RJC.2020.1345749

The protein data bank website (Internet). RCSB; 2019. (cited 2022 July 28). Available from: https://www.rcsb.org/structure/5IKR.

Morris GM, Huey R, Lindstrom W, et al. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J Comput Chem 2009;30:2785-91. DOI: https://doi.org/10.1002/jcc.21256

Castro-Alvarez A, Costa AM, Vilarrasa J. The Performance of Several Docking Programs at Reproducing Protein-Macrolide-Like Crystal Structures. Molecules 2017;22:136. DOI: https://doi.org/10.3390/molecules22010136

Pagadala NS, Syed K, Tuszynski J. Software for molecular docking: a review. Biophys Rev 2017;9:91-102. DOI: https://doi.org/10.1007/s12551-016-0247-1

Abdullah EC. E-pharmacophore mapping combined with virtual screening and molecular docking to identify potent and selective inhibitors of P90 ribosomal S6 kinase (RSK). Turk J Pharm Sci 2016;13:241-8.

Forli S, Huey R, Pique ME, et al. Computational protein-ligand docking and virtual drug screening with the AutoDock suite. Nat Protoc 2016;11:905-19. DOI: https://doi.org/10.1038/nprot.2016.051

Pratama MRF, Poerwono H, Siswandono S. Design and Molecular Docking of Novel 5-O-Benzoylpinostrobin Derivatives as Anti-Breast Cancer, Thai J Pharma Sci 2019;43:201-12.

Hevener KE, Zhao W, Ball DM, et al. Validation of molecular docking programs for virtual screening against dihydropteroate synthase. J Chem Inf Model 2009;49:444-60. DOI: https://doi.org/10.1021/ci800293n

Muttaqin F, Ismail H, Muhammad HN. Studi Molecular Docking, Molecular Dynamic, Dan Prediksi Toksisitas Senyawa Turunan Alkaloid Naftiridin Sebagai Inhibitor Protein Kasein Kinase 2-Α Pada Kanker Leukimia. Pharmacoscript 2019;2:131–51. DOI: https://doi.org/10.36423/pharmacoscript.v2i1.241

Noviardi H, Fachrurrazie. Potensi Senyawa Bullatalisin Sebagai Inhibitor Protein Leukotrien A4 Hidrolase Pada Kanker Kolon Secara In Silico. Fitofarmaka 2015;5:65–73. DOI: https://doi.org/10.33751/jf.v5i2.410

Arwansyah, Ambarsari L, Sumaryada T. Simulasi Docking Senyawa Kurkumin dan Analognya Sebagai Inhibitor Reseptor Androgen pada Kanker Prostat. Journal Current Biochemistry 2014;1. DOI: https://doi.org/10.29244/cb.1.1.11-19

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Published

16-03-2023

How to Cite

Wiyono, A. S., Siswandono, S., & Diyah, N. W. (2023). Molecular docking of 5-o-benzoylpinostrobin derivatives from <em>Boesenbergia pandurata</em> roxb. as anti-inflammatory. Journal of Public Health in Africa, 14(s1). https://doi.org/10.4081/jphia.2023.2532