Journal of Drug Design and Medicinal Chemistry

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Molecular Interaction Analysis of Phytochemicals as the Prospective Potential Multi-Target Inhibitors Related to Psoriasis and Other Autoimmune Disorders

Received: Jan. 02, 2024    Accepted: Jan. 20, 2024    Published: Feb. 01, 2024
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Abstract

Psoriasis is an inflammatory skin disease in which the immune system's T cells are activated and trigger inflammation within the skin. Inflammatory markers, such as IL-23, IL-17, IL-6, TNF-α, NLRP-3, and 12R Lipoxygenase (12 R-Lox), play a crucial role in the inflammatory pathway. Anti-inflammatory drugs are used to modulate the immune response and reduce excessive inflammation that contributes to disease progression. However, many existing anti-inflammatory drugs often target a single marker, potentially limiting their effectiveness and leading to side effects. Emerging research has highlighted the potential of various phytochemicals to modulate inflammatory processes and contribute to improved health outcomes. This study aimed to explore the potential of phytochemicals as alternative therapeutic agents targeting multiple psoriasis inflammatory biomarkers. In silico molecular docking was conducted on various phytochemicals, including curcumin, mangiferin, reservatrol, silybin, quercertin, piperine, and naringin against different inflammatory biomarkers: IL-6, IL-17, IL-23, TNF-α, NLRP-3 and 12R-Lox. The results illustrated that among the phytochemicals, silybin exhibited the highest docking score and inhibiting effects on all the inflammatory biomarkers. Curcumin, mangiferin, silybin and piperine demonstrated binding with multiple inflammatory biomarkers. Additionally, 12R-Lox displayed the highest binding affinity with all the phytochemicals. The inhibition and binding effects of the remaining phytochemicals under evaluation were moderate. The combination of these phytochemicals can be used for the preparation of medications targeting psoriasis.

DOI 10.11648/jddmc.20241001.14
Published in Journal of Drug Design and Medicinal Chemistry ( Volume 10, Issue 1, April 2024 )
Page(s) 16-30
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Psoriasis, Molecular Docking, Inflammatory Biomarkers, Pharmacokinetic

References
[1] Okin D, Medzhitov R. Evolution of inflammatory diseases. Curr Biol 2012; 22(17): R733-40. http://dx.doi.org/10.1016/j.cub.2012.07.029.
[2] Libby P. Inflammatory mechanisms: the molecular basis of inflammation and disease. Nutr Rev 2007; 65(suppl_3): S140-6. https://doi.org/10.1111/j.1753-4887.2007.tb00352.x.
[3] Sharma RK, Sharma MR, Mahendra A, Kumar S. Role of Inflammatory Cytokines in Pathophysiology of Psoriasis. Curr Pharmacol Rep 2022; 8: 99-105 https://doi.org/10.1007/s40495-021-00277-2.
[4] Hänsel A, Günther C, Ingwersen J, Starke J, Schmitz M, Bachmann M, Meurer M, Rieber EP, Schäkel K. Human slan (6-sulfo LacNAc) dendritic cells are inflammatory dermal dendritic cells in psoriasis and drive strong TH17/TH1 T-cell responses. J Allergy Clin Immunol 2011; 127(3): 787-94. https://doi.org/10.1016/j.jaci.2010.12.009.
[5] Brembilla NC, Senra L, Boehncke WH. The IL-17 family of cytokines in psoriasis: IL-17A and beyond. Front Immunol 2018; 9: 1682. https://doi.org/10.3389/fimmu.2018.01682.
[6] Blauvelt A. IL-6 differs from TNF-α: unpredicted clinical effects caused by IL-6 blockade in psoriasis. J Invest Dermatol 2017; 137(3): 541-2. https://doi.org/10.1016/j.jid.2016.11.022.
[7] Carlström M, Ekman AK, Petersson S, Söderkvist P, Enerbäck C. Genetic support for the role of the NLRP 3 inflammasome in psoriasis susceptibility. Exp Dermatol 2012; 21(12): 932-7. https://doi.org/10.1111/exd.12049.
[8] Bhuktar H, Shukla S, Kakularam KR, Battu S, Srikanth M, Srivastava S, et al. Design, synthesis and evaluation of 2-aryl quinoline derivatives against 12R-lipoxygenase (12R-LOX): Discovery of first inhibitor of 12R-LOX. Bioorg Chem 2023; 138: 106606. https://doi.org/10.1016/j.bioorg.2023.106606.
[9] Seeliger D, de Groot BL. Ligand docking and binding site analysis with PyMOL and Autodock/Vina. J Comput Aided Mol Des 2010; 24(5): 417-22. https://doi.org/10.1007/s10822-010-9352-6.
[10] Sharmila CM, Devi RC, Sureka A, MuthuKumar NJ, Banumathi V. In silico analysis of the effect of vasicine and vasinone against human tyrosinase receptor in the management of hyperpigmentation of skin diseases. Asian J Pharm Pharmacol 2019; 5: 518-24. https://doi.org/10.31024/ajpp.2019.5.3.13.
[11] Hussain J, Sali VK, Vasanthi HR. Natural Resources for Human Health. Age 2022; 56(60): 4. https://doi.org/10.53365/nrfhh/150494.
[12] Venkata M, Sripathy R, Anjana D, Somashekara N, Krishnaraju A, Krishanu S, Murali M, Verma SR, Ramchand CN. In silico, in vitro and in vivo assessment of safety and anti-inflammatory activity of curcumin. Am J Infect Dis 2012; 8(1): 26. http://dx.doi.org/10.3844/ajidsp.2012.26.33.
[13] Xie Y, Feng SL, Mai CT, Zheng YF, Wang H, Liu ZQ, et al. Suppression of up-regulated LXRα by silybin ameliorates experimental rheumatoid arthritis and abnormal lipid metabolism. Phytomedicine 2021; 80: 153339. https://doi.org/10.1016/j.phymed.2020.153339.
[14] Jones G, Willett P, Glen RC, Leach AR, Taylor R. Development and validation of a genetic algorithm for flexible docking. J Mol Biol 1997; 267(3): 727-48. https://doi.org/10.1006/jmbi.1996.0897.
[15] Irwin JJ, Shoichet BK. Docking screens for novel ligands conferring new biology: Miniperspective. J Med Chem 2016; 59(9): 4103-20. https://doi.org/10.1021/acs.jmedchem.5b02008.
[16] Mohanasundaram N, Sekhar T. Computational studies of molecular targets regarding the adverse effects of isoniazid drug for tuberculosis. Curr Pharmacogenomics Person Med 2018; 16(3): 210-8. https://doi.org/10.2174/1875692116666181108145230.
[17] Chunduri V, Maddi S. Role of in vitro two-dimensional (2D) and three-dimensional (3D) cell culture systems for ADME-Tox screening in drug discovery and development: a comprehensive review. ADMET DMPK 2023; 11(1): 1-32. https://doi.org/10.5599/admet.1513.
[18] Ashburn TT, Thor KB. Drug repositioning: identifying and developing new uses for existing drugs. Nat Rev Drug Discov 2004; 3(8): 673-83. https://doi.org/10.1038/nrd1468.
[19] Li J, Zheng S, Chen B, Butte AJ, Swamidass SJ, Lu Z. A survey of current trends in computational drug repositioning. Brief Bioinform 2016; 17(1): 2-12. https://doi.org/10.1093/bib/bbv020.
[20] Chopra G, Samudrala R. Exploring polypharmacology in drug discovery and repurposing using the CANDO platform. Curr Pharm Des 2016; 22(21): 3109-23. https://doi.org/10.2174/1381612822666160325121943.
[21] Zhang L, Lin D, Sun X, Curth U, Drosten C, Sauerhering L, et al. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors. Science 2020; 368(6489): 409-12. https://doi.org/10.1126/science.abb3405.
[22] Forli S, Huey R, Pique ME, Sanner MF, Goodsell DS, Olson AJ. Computational protein–ligand docking and virtual drug screening with the AutoDock suite. Nat Protoc 2016; 11(5): 905-19. https://doi.org/10.1038/nprot.2016.051.
[23] Ravindranath PA, Forli S, Goodsell DS, Olson AJ, Sanner MF. AutoDockFR: advances in protein-ligand docking with explicitly specified binding site flexibility. PLoS Comput Biol 2015; 11(12): e1004586. https://doi.org/10.1371/journal.pcbi.1004586.
[24] Oggu S, Akshinthala P, Katari NK, Nagarapu LK, Malempati S, Gundla R, Jonnalagadda SB. Design, synthesis, anticancer evaluation and molecular docking studies of 1,2,3-triazole incorporated 1,3,4-oxadiazole-Triazine derivatives. Heliyon. 2023 May 3; 9(5): e15935. doi: 10.1016/j.heliyon.2023.e15935.
[25] Cao D, Wang J, Zhou R, Li Y, Yu H, Hou T. ADMET evaluation in drug discovery. 11. PharmacoKinetics Knowledge Base (PKKB): a comprehensive database of pharmacokinetic and toxic properties for drugs. J Chem Inf Model 2012; 52(5): 1132-7. https://doi.org/10.1021/ci300112j.
[26] Daina A, Michielin O, Zoete V. iLOGP: a simple, robust, and efficient description of n-octanol/water partition coefficient for drug design using the GB/SA approach. J Chem Inf Model 2014; 54(12): 3284-301. https://doi.org/10.1021/ci500467k.
[27] Daina A, Zoete V. A boiled-egg to predict gastrointestinal absorption and brain penetration of small molecules. Chem Med Chem. 2016; 11(11): 1117-21. https://doi.org/10.1002/cmdc.201600182.
[28] Benfenati E, Benigni R, Demarini DM, Helma C, Kirkland D, Martin TM, et al. Predictive models for carcinogenicity and mutagenicity: frameworks, state-of-the-art, and perspectives. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 2009; 27(2): 57-90. https://doi.org/10.1080/10590500902885593.
[29] Lipinski CA. Lead-and drug-like compounds: the rule-of-five revolution. Drug Discov Today Technol 2004; 1(4): 337-41. https://doi.org/10.1016/j.ddtec.2004.11.007.
[30] Halder P, Pal U, Paladhi P, Dutta S, Paul P, Pal S, et al. Evaluation of potency of the selected bioactive molecules from Indian medicinal plants with MPro of SARS-CoV-2 through in silico analysis. J Ayurveda Integr Med 2022; 13(2): 100449. https://doi.org/10.1016/j.jaim.2021.05.003.
[31] Choudhury A, Das NC, Patra R, Bhattacharya M, Ghosh P, Patra BC, et al. Exploring the binding efficacy of ivermectin against the key proteins of SARS-CoV-2 pathogenesis: an in silico approach. Future Virol 2021; 16(4): 277-91. https://doi.org/10.2217/fvl-2020-0342.
[32] Shaik B, Eerla A, Palatheeya S, Veerareddy PR, Maddi S. A Validated HPLC Method for the Simultaneous Quantification of Curcumin, Silybin, and Psoralen: Application to Phytopharmaceuticals. Rev Bras Farmacogn 2023; 33: 610-616. https://doi.org/10.1007/s43450-023-00392-9.
[33] Benet LZ, Hosey CM, Ursu O, Oprea TI. BDDCS, the Rule of 5 and drugability. Adv Drug Deliv Rev 2016; 101: 89-98. https://doi.org/10.1016/j.addr.2016.05.007.
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  • APA Style

    Swain, B., Maddi, S. (2024). Molecular Interaction Analysis of Phytochemicals as the Prospective Potential Multi-Target Inhibitors Related to Psoriasis and Other Autoimmune Disorders. Journal of Drug Design and Medicinal Chemistry, 10(1), 16-30. https://doi.org/10.11648/jddmc.20241001.14

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    Swain, B.; Maddi, S. Molecular Interaction Analysis of Phytochemicals as the Prospective Potential Multi-Target Inhibitors Related to Psoriasis and Other Autoimmune Disorders. J. Drug Des. Med. Chem. 2024, 10(1), 16-30. doi: 10.11648/jddmc.20241001.14

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    AMA Style

    Swain B, Maddi S. Molecular Interaction Analysis of Phytochemicals as the Prospective Potential Multi-Target Inhibitors Related to Psoriasis and Other Autoimmune Disorders. J Drug Des Med Chem. 2024;10(1):16-30. doi: 10.11648/jddmc.20241001.14

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  • @article{10.11648/jddmc.20241001.14,
      author = {Biswajit Swain and Srinivas Maddi},
      title = {Molecular Interaction Analysis of Phytochemicals as the Prospective Potential Multi-Target Inhibitors Related to Psoriasis and Other Autoimmune Disorders},
      journal = {Journal of Drug Design and Medicinal Chemistry},
      volume = {10},
      number = {1},
      pages = {16-30},
      doi = {10.11648/jddmc.20241001.14},
      url = {https://doi.org/10.11648/jddmc.20241001.14},
      eprint = {https://download.sciencepg.com/pdf/10.11648.jddmc.20241001.14},
      abstract = {Psoriasis is an inflammatory skin disease in which the immune system's T cells are activated and trigger inflammation within the skin. Inflammatory markers, such as IL-23, IL-17, IL-6, TNF-α, NLRP-3, and 12R Lipoxygenase (12 R-Lox), play a crucial role in the inflammatory pathway. Anti-inflammatory drugs are used to modulate the immune response and reduce excessive inflammation that contributes to disease progression. However, many existing anti-inflammatory drugs often target a single marker, potentially limiting their effectiveness and leading to side effects. Emerging research has highlighted the potential of various phytochemicals to modulate inflammatory processes and contribute to improved health outcomes. This study aimed to explore the potential of phytochemicals as alternative therapeutic agents targeting multiple psoriasis inflammatory biomarkers. In silico molecular docking was conducted on various phytochemicals, including curcumin, mangiferin, reservatrol, silybin, quercertin, piperine, and naringin against different inflammatory biomarkers: IL-6, IL-17, IL-23, TNF-α, NLRP-3 and 12R-Lox. The results illustrated that among the phytochemicals, silybin exhibited the highest docking score and inhibiting effects on all the inflammatory biomarkers. Curcumin, mangiferin, silybin and piperine demonstrated binding with multiple inflammatory biomarkers. Additionally, 12R-Lox displayed the highest binding affinity with all the phytochemicals. The inhibition and binding effects of the remaining phytochemicals under evaluation were moderate. The combination of these phytochemicals can be used for the preparation of medications targeting psoriasis.
    },
     year = {2024}
    }
    

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    T1  - Molecular Interaction Analysis of Phytochemicals as the Prospective Potential Multi-Target Inhibitors Related to Psoriasis and Other Autoimmune Disorders
    AU  - Biswajit Swain
    AU  - Srinivas Maddi
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    JF  - Journal of Drug Design and Medicinal Chemistry
    JO  - Journal of Drug Design and Medicinal Chemistry
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    UR  - https://doi.org/10.11648/jddmc.20241001.14
    AB  - Psoriasis is an inflammatory skin disease in which the immune system's T cells are activated and trigger inflammation within the skin. Inflammatory markers, such as IL-23, IL-17, IL-6, TNF-α, NLRP-3, and 12R Lipoxygenase (12 R-Lox), play a crucial role in the inflammatory pathway. Anti-inflammatory drugs are used to modulate the immune response and reduce excessive inflammation that contributes to disease progression. However, many existing anti-inflammatory drugs often target a single marker, potentially limiting their effectiveness and leading to side effects. Emerging research has highlighted the potential of various phytochemicals to modulate inflammatory processes and contribute to improved health outcomes. This study aimed to explore the potential of phytochemicals as alternative therapeutic agents targeting multiple psoriasis inflammatory biomarkers. In silico molecular docking was conducted on various phytochemicals, including curcumin, mangiferin, reservatrol, silybin, quercertin, piperine, and naringin against different inflammatory biomarkers: IL-6, IL-17, IL-23, TNF-α, NLRP-3 and 12R-Lox. The results illustrated that among the phytochemicals, silybin exhibited the highest docking score and inhibiting effects on all the inflammatory biomarkers. Curcumin, mangiferin, silybin and piperine demonstrated binding with multiple inflammatory biomarkers. Additionally, 12R-Lox displayed the highest binding affinity with all the phytochemicals. The inhibition and binding effects of the remaining phytochemicals under evaluation were moderate. The combination of these phytochemicals can be used for the preparation of medications targeting psoriasis.
    
    VL  - 10
    IS  - 1
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Author Information
  • Acubiosys Private Limited, Telangana State Industrial Infrastructure Corporation Limited (TSIIC-IALA) - Industrial Area Local Authority, Hyderabad, India

  • Acubiosys Private Limited, Telangana State Industrial Infrastructure Corporation Limited (TSIIC-IALA) - Industrial Area Local Authority, Hyderabad, India

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