IN SILICO STUDY OF BIOACTIVE COMPOUNDS FROM SUNGKAI (PERONEMA CANESCENS) AS IMMUNOMODULATOR

MUHAMMAD RYAN RADIX RAHARDHIAN; YASMIWAR SUSILAWATI; IDA MUSFIROH; RADEN MAYA FEBRIYANTI; MUCHTARIDI; SRI ADI SUMIWI

doi:10.22159/ijap.2022.v14s4.PP33

Authors

MUHAMMAD RYAN RADIX RAHARDHIAN Doctor Program, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor 45363, Indonesia, Department of Pharmaceutical Biology, Semarang College of Pharmaceutical Sciences (STIFAR), Semarang 50192, Indonesia
YASMIWAR SUSILAWATI Department of Pharmaceutical Biology, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor 45363, Indonesia
IDA MUSFIROH Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor 45363, Indonesia
RADEN MAYA FEBRIYANTI Department of Pharmaceutical Biology, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor 45363, Indonesia
MUCHTARIDI Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor 45363, Indonesia
SRI ADI SUMIWI Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Padjadjaran University, Jatinangor 45363, Indonesia

DOI:

https://doi.org/10.22159/ijap.2022.v14s4.PP33

Keywords:

Sungkai, Peronemin, IL-6, TNF-α, Immunomodulatory, COVID-19, In silico

Abstract

Objective: This study aims to predict a bioactive compound from Peronema canescens (PC) with mechanisms inhibitor interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) potential as an immunomodulatory using in silico approach.

Methods: Autodock 4 was used to accomplish computer-assisted drug design with molecular docking simulation to discover binding energy, inhibition constant, and interactions with an amino acid in bioactive compounds from PC against IL-6 and TNF-α receptors. Lipinski predicts the drug-likeness of a bioactive compound for the oral route of administration. ADMET profiling of bioactive compounds to predict pharmacokinetic properties with pkCSM ADMET.

Results: The results showed that the best binding energy, inhibition constant, and interactions with an amino acid of peronemin C1 against IL-6 and TNF-α receptors were (-7.19 kcal/mol; 5.39 nM; Arg 179, Arg 182, Gln 175), and (-8.86 kcal/mol; 320.42 nM; Tyr 119, Tyr 59, and Gly 121), respectively. All bioactive compounds from PC met Lipinski's rule of five requirements for oral administration. ADMET prediction results all bioactive compounds from PC are non-mutagenic, except peronemin D1 is mutagenic.

Conclusion: The peronemin C1 bioactive compounds from PC have good immunomodulatory potential, effectively inhibiting human IL-6 and TNF-α receptors using in silico approach.

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References

Guo Y, Hu K, Li Y, Lu C, Ling K, Cai C. Targeting TNF-α for COVID-19: recent advanced and controversies. Front Public Health. 2022;10:833967. doi: 10.3389/fpubh.2022.833967, PMID 35223745.

National Institutes of Health. Treatment Guidelines Panel. Coronavirus disease. Vol. 2021. National Institutes of Health; 2019. p. 1-243.

Yuandani, Jantan I, Rohani AS, Sumantri IB. Immunomodulatory effects and mechanisms of curcuma species and their bioactive compounds: a review. Front Pharmacol. 2021;12:643119. doi: 10.3389/fphar.2021.643119. PMID 33995049.

Saroj P, Verma M, Jha KK, Pal M. An overview on immunomodulation. Adv Sci Res. 2012;3(1):7-12.

Opal SM, DePalo VA. Anti-inflammatory cytokines. Chest. 2000;117(4):1162-72. doi: 10.1378/chest.117.4.1162, PMID 10767254.

Nasonov E, Samsonov M. The role of interleukin 6 inhibitors in therapy of severe COVID-19. Biomed Pharmacother. 2020;131:110698. doi: 10.1016/j.biopha.2020.110698, PMID 32920514.

Tanaka T, Narazaki M, Kishimoto T. IL-6. In: Inflammation, immunity, and disease. Cold Spring Harb lab Press. Vol. 6; 2014. p. 1-16.

Kalliolias GD, Ivashkiv LB. TNF biology, pathogenic mechanisms and emerging therapeutic strategies. Nat Rev Rheumatol. 2016;12(1):49-62. doi: 10.1038/nrrheum.2015.169, PMID 26656660.

Ang L, Song E, Lee HW, Lee MS. Herbal medicine for the treatment of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis of randomized controlled trials. J Clin Med. 2020;9(5):1-20. doi: 10.3390/jcm9051583, PMID 32456123.

Rahman A, Rengganis GP, Prayuni S, Novriyanti I, Sari TN, Pratiwi PD. The effect of sungkai leaves (Peronema canescens) infusion on the number of leukocytes in mice. J Healthc Technol Med. 2021;7(2):614-20.

Pinzi L, Rastelli G. Molecular docking: shifting paradigms in drug discovery. Int J Mol Sci. 2019;20(18). doi: 10.3390/ijms20184331, PMID 31487867.

Wang SQ, Shi M, Fang L, Xu SM, Wang C, Yu ZX. Design of dual inhibitors of human TNF-α and IL-6 with potentials for the treatment of rheumatoid arthritis. Trop J Pharm Res. 2019;18(11):2305-12.

Morris GM, Huey R, Olson AJ. Using AutoDock for ligand-receptor docking. Curr Protoc Bioinformatics. 2008;8:8.14. doi: 10.1002/0471250953.bi0814s24, PMID 19085980.

Biovia DS. Discovery studio modeling environment. Dassault Syst; 2021.

Kitagawa I, Simanjuntak P, Hori K, Nagami N, Mahmud T, Shibuya H. Indonesian medicinal plants. VII. Seven new clerodane-type diterpenoids, peronemins. Chem Pharm Bull. 1994;57(534):364–70.

PerkinElmer, ChemDraw I 15. User Guide. 2015;168.

Somers W, Stahl M, Seehra JS. 1.9 Å crystal structure of interleukin 6: implications for a novel mode of receptor dimerization and signaling. EMBO J. 1997;16(5):989-97. doi: 10.1093/emboj/16.5.989, PMID 9118960.

He MM, Smith AS, Oslob JD, Flanagan WM, Braisted AC, Whitty A. Small-molecule inhibition of TNF-α. Science Magscience Mag. 2005;310:1022-5.

Zubair MS, Maulana S, Mukaddas A. Molecular docking and molecular dynamics simulation of compounds from nigella genus on protease HIV-1 enzyme inhibitors. Galen J Pharm. 2020;6(1):132-40.

Muchtaridi M, Dermawan D, Yusuf M. Molecular docking, 3D structure-based pharmacophore modeling, and ADME prediction of alpha mangostin and its derivatives against estrogen receptor alpha. J Young Pharm. 2018;10(3):252-9. doi: 10.5530/jyp.2018.10.58.

Lipinski CA. Lead- and drug-like compounds: the rule-of-five revolution. Drug Discov Today Technol. 2004;1(4):337-41. doi: 10.1016/j.ddtec.2004.11.007, PMID 24981612.

DE Pires V, Blundell TL. Ascher DB. pkCSM: predicting small-molecule pharmacokinetic properties using graph-based signatures (Theory-How to Enterpret pkCSM Result). pKCSM. 2015;5.

Holik HA, Ibrahim FM, Wianatalie E, Achmad A, Faried A, Kartamihardja AHS. The molecular interaction and ADMET prediction of modified Jph203 as a potential radiopharmaceutical kit for molecular imaging of cancer: an in silico research. Int J App Pharm. 2021;13(4):205-9. doi: 10.22159/ijap.2021.v13s4.43860.

Forlemu N, Watkins P, Sloop J. Molecular docking of selective binding affinity of sulfonamide derivatives as potential antimalarial agents targeting the glycolytic enzymes: GAPDH, aldolase and TPI. OJBIPHY. 2017;7(1):41-57. doi: 10.4236/ojbiphy.2017.71004.

Azzahra RW, Murdaya N, Al Shofwan AA, Ramadan E, Utami SD. Molecular docking compounds ethanol extract of Kenikir leaves (Cosmos caudatus) as IL-6 inhibitor in an inflammatory response. J Farm Udayana. 2021;10(2):138.

Zhou W, Cai JF, Yuan F, Ma M, Yin F. In silico targeting of interleukin-6 by natural compounds. Bangladesh J Pharmacol. 2014;9(3):371-6. doi: 10.3329/bjp.v9i3.19065.

Malik A, Naz A, Ahmad S, Hafeez M, Awan FM, Jafar TH. Inhibitory potential of phytochemicals on interleukin-6-mediated T-cell reduction in COVID-19 patients: A computational approach. Bioinform Biol Insights. 2021;15:11779322211021430. doi: 10.1177/11779322211021430, PMID 34163151.

Fatimawali F, Marko Jeremia K, Siboantua Broolin S, Tri Andira H, Billy Johnson K, Trina Ekawati T. Immunomodulatory potential of bioactive compounds of betel leaf extract targeting COVID-19 immunological human host proteins: an in silico study. J App Pharm Sci. 2022;12(2):75-88. doi: 10.7324/JAPS.2021.120208.

Zia K, Ashraf S, Jabeen A, Saeed M, Nur-e-Alam M, Ahmed S. Identification of potential TNF-α inhibitors: from in silico to in vitro studies. Sci Rep. 2020;10(1):20974. doi: 10.1038/s41598-020-77750-3, PMID 33262408.

Kim OTP, Le MD, Trinh HX, Nong HV. In silico studies for the interaction of tumor necrosis factor-alpha (TNF-α) with different saponins from vietnamese ginseng (Panax vietnamesis). Biophys Physicobiol. 2016;13:173-80. doi: 10.2142/biophysico.13.0_173, PMID 27924272.

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 Deliv Rev. 2001;46(1-3):3-26. doi: 10.1016/s0169-409x(00)00129-0, PMID 11259830.