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Volume: 9, Issue: 7, July, 2019
DOI: 10.7324/JAPS.2019.90703

Research Article

In silico molecular docking and ADME/T analysis of plant compounds against IL17A and IL18 targets in gouty arthritis

Sowmya Hari

  Author Affiliations


Accumulation of urate crystals and subsequent inflammation are the major cause of pathogenesis of gout. Two pro inflammatory cytokines IL17A and IL18 are upregulated in the serum of gout patients and plays a major role in promoting inflammation. Inhibition of these cytokines by plant phytochemicals would reduce the severity of inflammation in gout. In the present study, in silico analysis of inhibition of IL17A and IL18 by 10 plant phytochemicals were studied using the AutoDock 4.2 based on the principles of Lamarckian genetic algorithm. The results revealed a binding energy in the range of −6.32 kcal/mol to −3.5 kcal/mol and interacted with the amino acids in active pocket of IL17A and IL18. Among all the compounds, syringaresinol showing the least binding energy of −6.05 kcal/mol with IL17A and −6.32 kcal/mol with IL18. The control drug, allopurinol showed a binding energy of −3.32 and −3.18 kcal/mol with IL17A and IL18, respectively. In addition, ADME/T properties of the compounds were also analyzed to predict their drug likeliness. This docking study can be used for developing potent inhibitors of IL17A and IL18 for the treatment of gout.


Gout, IL17A, IL18, in silico, AutoDock, ADME/T.

Citation: Hari S. In silico molecular docking and ADME/T analysis of plant compounds against IL17A and IL18 targets in gouty arthritis. J Appl Pharm Sci, 2019; 9(07):018–026.

Copyright: The Author(s). This is an open access article distributed under the Creative Commons Attribution Non-Commercial License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Adejoro IA, Waheed SO, Adeboye OO. Molecular docking studies of Lonchocarpus cyanescens triterpenoids as inhibitors for malaria. J Phys Chem Biophys, 2016; 6(2):1-4. https://doi.org/10.4172/2161-0398.1000213

Afriza D, Suriyah WH, Ichwan SJ. In silico analysis of molecular interactions between the anti-apoptotic protein survivin and dentatin, nordentatin, and quercetin. J Phys Conf Ser, 2018; 1073(3):1-7. https://doi.org/10.1088/1742-6596/1073/3/032001

Azam SS, Abbasi SW. Molecular docking studies for the identification of novel melatoninergic inhibitors for acetylserotonin- O-methyltransferase using different docking routines. TBioMed, 2013; 10(1):1-16. https://doi.org/10.1186/1742-4682-10-63

Bajpai VK, Alam MB, Quan KT, Ju MK, Majumder R, Shukla S, Huh YS, Na M, Lee SH, Han YK. Attenuation of inflammatory responses by (+)-syringaresinol via MAP-Kinase-mediated suppression of NF-κB signaling in vitro and in vivo. Sci Rep, 2018; 8(1):9216:1-10. https://doi.org/10.1038/s41598-018-27585-w

Cavalcanti NG, Marques CD, Lins e Lins TU, Pereira MC, Rêgo MJ, Duarte AL, Pitta ID, Pitta MG. Cytokine profile in gout: inflammation driven by IL-6 and IL-18? Immunol Invest, 2016; 45(5):383-95. https://doi.org/10.3109/08820139.2016.1153651

Chandrashekhar VM, Ganapaty S, Ramkishan A, Narsu ML. Neuroprotective activity of gossypin from Hibiscus vitifolius against global cerebral ischemia model in rats. Indian J Pharmacol, 2013; 45(6):575. https://doi.org/10.4103/0253-7613.121367

Cheng F, Li W, Zhou Y, Shen J, Wu Z, Liu G, Lee PW, Tang Y. admetSAR: a comprehensive source and free tool for assessment of chemical ADMET properties. J Chem Inf Model, 2012; 3099-105. https://doi.org/10.1021/ci300367a

Chiu CC, Chen CH, Huang MC, Chen PY, Tsai CJ, Lu ML. The relationship between serum uric acid concentration and metabolic syndrome in patients with schizophrenia or schizoaffective disorder, J Clin Psychopharmacol, 2012; 32(5):585-92. https://doi.org/10.1097/JCP.0b013e3182664e64

Chung BH, Kim S, Kim JD, Lee JJ, Baek YY, Jeoung D, Lee H, Choe J, Ha KS, Won MH, Kwon YG. Syringaresinol causes vasorelaxation by elevating nitric oxide production through the phosphorylation and dimerization of endothelial nitric oxide synthase. Exp Mol Med, 2012; 44(3):191. https://doi.org/10.3858/emm.2012.44.3.014

Dai J, Li N, Wang J, Schneider U. Fruitful decades for canthin-6- ones from 1952 to 2015: biosynthesis, chemistry, and biological activities. Molecules, 2016; 21(4):493. https://doi.org/10.3390/molecules21040493

de Andrade JA, Gayer CR, de Almeida Nogueira NP, Paes MC, Bastos VL, Neto JD, Alves SC, Coelho RM, da Cunha MG, Gomes RN, Águila MB. The effect of thiamine deficiency on inflammation, oxidative stress and cellular migration in an experimental model of sepsis. J Inflamm, 2014; 11(1):11. https://doi.org/10.1186/1476-9255-11-11

Doherty M. New insights into the epidemiology of gout. Rheumatology, 2009; 48:ii2-8. https://doi.org/10.1093/rheumatology/kep086

Dundas J, Ouyang Z, Tseng J, Binkowski A, Turpaz Y, Liang J. CASTp: computed atlas of surface topography of proteins with structural and topographical mapping of functionally annotated residues. Nucleic Acids Res, 2006; 34(suppl_2):W116-8. https://doi.org/10.1093/nar/gkl282

El Ridi R, Tallima H. Physiological functions and pathogenic potential of uric acid: a review. J Adv Res, 2017; 8(5):487-93. https://doi.org/10.1016/j.jare.2017.03.003

Feig DI, Kang DH, Johnson RJ. Uric acid and cardiovascular risk. N Engl J Med, 2008; 359(17):1811-21. https://doi.org/10.1056/NEJMra0800885

Frieder J, Kivelevitch D, Menter A. Secukinumab: a review of the anti-IL-17A biologic for the treatment of psoriasis. Ther Adv Chronic Dis, 2018; 9(1):5-21. https://doi.org/10.1177/2040622317738910

Gerald F and Falasca MD. Metabolic diseases: gout. Clin. Dermatol, 2006; 24(6):498-508. https://doi.org/10.1016/j.clindermatol.2006.07.015

Gholijani N, Gharagozloo M, Farjadian S, Amirghofran Z. Modulatory effects of thymol and carvacrol on inflammatory transcription factors in lipopolysaccharide-treated macrophages. J Immunotoxicol, 2016; 13(2):157-6. https://doi.org/10.3109/1547691X.2015.1029145

Grayson PC, Kim SY, LaValley M, Choi HK. Hyperuricemia and incident hypertension: a systematic review and meta-analysis. Arthritis Care Res (Hoboken), 2011; 63(1):102-10. https://doi.org/10.1002/acr.20344

Huang YH, Rose PW, Hsu CN. Citing a data repository: a case study of the protein data bank. PloS one, 2015; 10(8):e0136631. https://doi.org/10.1371/journal.pone.0136631

Karunakar P, Girija CR, Krishnamurthy V, Krishna V, Shivakumar KV. In silico antitubercular activity analysis of benzofuran and naphthofuran derivatives. Tuberc Res Treat, 2014; 2014:1-10. https://doi.org/10.1155/2014/697532

Kemmish H, Fasnacht M, Yan L. Fully automated antibody structure prediction using BIOVIA tools: validation study. PLoS One, 2017; 12(5):1-26. https://doi.org/10.1371/journal.pone.0177923

Kim S, Thiessen PA, Bolton EE, Chen J, Fu G, Gindulyte A, Han L, He J, He S, Shoemaker BA, Wang J. PubChem substance and compound databases. Nucleic Acids Res, 2015; 44(D1):D1202-13. https://doi.org/10.1093/nar/gkv951

Kirkham BW, Kavanaugh A, Reich K. Interleukin-17A: a unique pathway in immune-mediated diseases: psoriasis, psoriatic arthritis and rheumatoid arthritis. Immunology, 2014; 141(2):133-42. https://doi.org/10.1111/imm.12142

Kostalova E, Pavelka K, Vlaskova H, Musalkova D, Stiburkova B. Hyperuricemia and gout due to deficiency of hypoxanthine-guanine phosphoribosyltransferase in female carriers: new insight to differential diagnosis. Clin Chim Acta, 2015; 440:214-7. https://doi.org/10.1016/j.cca.2014.11.026

Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliver Rev, 2012; 64:4-17. https://doi.org/10.1016/j.addr.2012.09.019

Liu Y, Zhao Q, Yin Y, McNutt MA, Zhang T, Cao Y. Serum levels of IL-17 are elevated in patients with acute gouty arthritis. Biochem Biophys Res Commun, 2018; 497(3):897-902. https://doi.org/10.1016/j.bbrc.2018.02.166

Marashly ET, Bohlega SA. Riboflavin has neuroprotective potential: focus on Parkinson's disease and migraine. Front Neurol, 2017; 8:333. https://doi.org/10.3389/fneur.2017.00333

Meenambiga SS, Venkataraghavan R, Biswal RA. In silico analysis of plant phytochemicals against secreted aspartic proteinase enzyme of Candida albicans. J Appl Pharm Sci, 2018; 8(11):140-50. https://doi.org/10.7324/JAPS.2018.81120

Mohandas R, Johnson RJ. Uric acid levels increase risk for new-onset kidney disease. J Am Soc Nephrol, 2008; 19(12):2251-3. https://doi.org/10.1681/ASN.2008091012

Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK, Olson AJ. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J Comput Chem, 1998; 19(14):1639-62. https://doi.org/10.1002/(SICI)1096-987X(19981115)19:14< 1639::AID-JCC10>3.0.CO;2-B

Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ. AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem, 2009; 30(16):2785-91. https://doi.org/10.1002/jcc.21256

Naghdi Badi H, Abdollahi M, Mehrafarin A, Ghorbanpour M, Tolyat M, Qaderi A, Ghiaci Yekta M. An overview on two valuable natural and bioactive compounds, thymol and carvacrol, in medicinal plants. J Med Plant Res, 2017; 3(63):1-32.

Ragab G, Elshahaly M, Bardin T. Gout: an old disease in new perspective-a review. J Adv Res, 2017; 8(5):495-511. https://doi.org/10.1016/j.jare.2017.04.008

Roddy E, Doherty M. Epidemiology of gout. Arthritis Res Ther, 2010; 12(223):1-11. https://doi.org/10.1186/ar3199

Saigal R, Agrawal A. Pathogenesis and clinical management of gouty arthritis. J Assoc Physicians India, 2015; 63:56-63.

Sedimbi SK, Hägglöf T, Karlsson MC. IL-18 in inflammatory and autoimmune disease. Cell Mol Life Sci, 2013; 70(24):4795-808. https://doi.org/10.1007/s00018-013-1425-y

Shi LS, Wu CH, Yang TC, Yao CW, Lin HC, Chang WL. Cytotoxic effect of triterpenoids from the root bark of Hibiscus syriacus. Fitoterapia, 2014; 97:184-91. https://doi.org/10.1016/j.fitote.2014.05.006

Soltani Z, Rasheed K, Kapusta DR, Reisin E. Potential role of uric acid in metabolic syndrome, hypertension, kidney injury, and cardiovascular diseases: is it time for reappraisal? Curr Hypertens Rep, 2013; 15(3):175-81. https://doi.org/10.1007/s11906-013-0344-5

Soumyakrishnan S, Sudhandiran G. Daidzein attenuates inflammation and exhibits antifibrotic effect against Bleomycin-induced pulmonary fibrosis in Wistar rats. Biomed Prev Nutr, 2011; 1(4):236-44. https://doi.org/10.1016/j.bionut.2011.09.005

Sun MY, Ye Y, Xiao L, Rahman K, Xia W, Zhang H. Daidzein: a review of pharmacological effects. Afr J Tradit Complement Altern Med, 2016; 3(3):117-32. https://doi.org/10.4314/ajtcam.v13i3.15

Verdrengh M, Jonsson IM, Holmdahl R, Tarkowski A. Genistein as an anti-inflammatory agent. Inflamm Res, 2003; 52(8):341-6. https://doi.org/10.1007/s00011-003-1182-8

Yuan S, Chan HS, Hu Z. Using PyMOL as a platform for computational drug design. Wiley interdisciplinary reviews. Comput Mol Sci, 2017; 7(2):e1298. https://doi.org/10.1002/wcms.1298

Zhou Z, Li X, Li H, Guo M, Liu S, Li C. Genetic analysis of IL- 17 gene polymorphisms in gout in a male Chinese Han population. PLoS One, 2016; 11(2):e0148082. https://doi.org/10.1371/journal.pone.0148082

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