IN SILICO STUDY OF CHEMICAL COMPOUNDS FROM ARECA NUT (ARECA CATECHU L.) ON GABAA RECEPTOR AS ANTI-INSOMNIA CANDIDATES

RESMI MUSTARICHIE; SANDRA MEGANTARA; NYI MEKAR SAPTARINI; SARAH HUSNA HAYATI

doi:10.22159/ijap.2022.v14s5.15

Authors

RESMI MUSTARICHIE Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Indonesia, 45363
SANDRA MEGANTARA Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Indonesia, 45363
NYI MEKAR SAPTARINI Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Indonesia, 45363
SARAH HUSNA HAYATI Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Indonesia, 45363

DOI:

https://doi.org/10.22159/ijap.2022.v14s5.15

Keywords:

Insomnia, Areca nut, Molecular docking, ADMET prediction

Abstract

Objective: In silico study of chemical compounds from areca nut (Areca catechu) on GABA_A receptor as anti-insomnia candidates.

Methods: Prediction and molecular docking of chemical compounds from areca nut with GABA_A receptors to find out which compounds are most likely to be anti-insomnia therapy candidates.

Results: Molecular docking with AutoDock Vina and ADMET prediction via PreADMET website. Molecular docking and ADME predictions show that there is one potential anti-insomnia compound called syringic acid that has the most amino acid residues in common with the native ligand and standard drug compared to other compounds, as well as producing free energy (ΔG) and inhibition constants (Ki) lower than the native ligand. Syringic acid also has a weak bond with plasma proteins. However, in the parameters of toxicity, syringic acid exhibits carcinogenic and mutagenic properties.

Conclusion: Based on the results of molecular docking and ADME prediction obtained one compound with the best results can be used as a candidate for anti-insomnia drugs, namely syringic acid.

Downloads

Download data is not yet available.

References

American Psychiatric Association. Diagnostic and statistical manual of mental disorders: sleep-wake disorders; 2013.

Sateia MJ, Sherrill WC, Winter Rosenberg C, Heald JL. Payer perspective of the american academy of sleep medicine clinical practice guideline for the pharmacologic treatment of chronic insomnia. J Clin Sleep Med. 2017;13(2):155-7. doi: 10.5664/jcsm.6428, PMID 28095976.

Medicine AA S. Sleep disorders medicine: basic science, technical considerations and clinical aspects: international classification of sleep disorders. 4th ed; 2014.

Riemann D, Voderholzer U. Primary insomnia: A risk factor to develop depression? J Affect Disord. 2003;76(1-3):255-9. doi: 10.1016/S0165-0327(02)00072-1, PMID 12943956.

Sleep-Wake Disorders Pharmacotherapy: A Pathophysiologic Approach, 11e Access Pharmacy McGraw; 2022.

Lufiyani I, Zahra AN, Yona S. Factors related to insomnia among end-stage renal disease patients on hemodialysis in Jakarta, Indonesia. Enfermeria Clinica. 2019;29:331-5. doi: 10.1016/j.enfcli.2019.04.141.

Kusuma H, Ropyanto CB, Widyaningsih S, Sujianto U. Relating factors of insomnia among haemodialysis patients. Nurs Med J Nursing 2018;8(1). doi: 10.14710/nmjn.v8i1.15741.

Wang Y, Zhu LY, Ma YF, Bo HX, Deng HB, Cao J. Association of insomnia disorder with sociodemographic factors and poor mental health in COVID-19 inpatients in China. Sleep Med. 2020;75:282-6. doi: 10.1016/j.sleep.2020.06.011. PMID 32919351.

Rogers BG, Bainter SA, Smith Alvarez R, Wohlgemuth WK, Antoni MH, Rodriguez AE. Insomnia, health, and health-related quality of life in an urban clinic sample of people living with HIV/AIDS. Behav Sleep Med. 2021;19(4):516-32. doi: 10.1080/15402002.2020.1803871, PMID 32781842.

Prabowo H, Dewi MP, Nadia. Intercorrelation of Insomnia, Sleep Duration, Internet Use Duration and Internet Addiction on Millennial in Jakarta. Presented at: 2020.

Centers for Disease Control and Prevention (US). C for DC and P. Short Sleep duration among US adults. Published online; 2022. https://www.cdc.gov/sleep/data_statistics.html.

Winkelman JW, Buxton OM, Jensen JE, Benson KL, O’Connor SP, Wang W. Reduced brain GABA in primary insomnia: preliminary data from 4T proton magnetic resonance spectroscopy (1H-MRS). Sleep. 2008;31(11):1499-506. doi: 10.1093/sleep/31.11.1499, PMID 19014069.

Goetz T, Arslan A, Wisden W, Wulff P. GABA(A) receptors: structure and function in the basal ganglia. Prog Brain Res. 2007;160:21-41. doi: 10.1016/S0079-6123(06)60003-4, PMID 17499107.

Bohm S, Grossmann V, Strulik H. R&D-driven medical progress, health care costs, and the future of human longevity. J Econ Ageing. 2021;18. doi: 10.1016/j.jeoa.2020.100286.

Meutia Sari L. Antioxidant activity of areca nut to human health: effect on oral cancer cell lines and immunomodulatory activity. Bioactive compounds in nutraceutical and functional food for good human health. Published online; 2021. doi: 10.5772/INTECHOPEN.96036.

Meti V, N KK, Professor Ra. Anxiolytic and ANTI depressant activity of areca catechu linn. In: Mice. World Journal of Pharmaceutical Research 2014;5(10);1367-76.

Shin HK, Kang YM, No KT. Predicting adme properties of chemicals. Handbook of computational chemistry. Published Online. 2017:2265-301. doi: 10.1007/978-3-319-27282-5_59.

Peng W, Liu Y, Zhao C, Huang X, Wu N, Hu M. In silico assessment of drug-like properties of alkaloids from Areca catechu L nut. Trop J Pharm Res 2015;14(4). doi: 10.4314/tjpr.v14i4.11.

Bouayyadi A, Aliani AE, Kasmi Y, Moussaif A, Abbadi NE, Mesfioui A. Molecular docking analysis of α2-containing GABAA receptors with benzimidazoles derivatives. Bio information. 2020;16(8):611-9. doi: 10.6026/97320630016611, PMID 33214749.

Miller PS, Aricescu AR. Crystal structure of a human GABAA receptor. Nature. 2014;512(7514):270-5. doi: 10.1038/NATURE13293, PMID 24909990.

Alhumaydhi FA, Rauf A, Rashid U, Bawazeer S, Khan K, Mubarak MS. In vivo and in silico studies of flavonoids isolated from pistacia integerrima as potential antidiarrheal agents. ACS Omega. 2021;6(24):15617-24. doi: 10.1021/acsomega.1c00298, PMID 34179606.

PreADMET–BMDRC. Available from: http://www.bmdrc.org/preadmet. [Last accessed on 08 Nov 2022]

Dermawan D, Sumirtanurdin R, Dewantisari D. Molecular dynamics simulation estrogen receptor alpha againts andrographolide as Anti Breast Cancer. Indonesian J Pharm Sci Technol. 2019;6(2):65-76. doi: 10.24198/ijpst.v6i2.18168.

Fakih TM, Putri NWRP, Marillia V, Ramadhan DSF, Darusman F. Identifikasi aktivitas biologis, prediksi toksisitas, dan molecular docking senyawa jubanine dari tanaman bidara arab sebagai kandidat antivirus SARS-CoV-2. J Ris Kim. 2022;13(1):111-21. doi: 10.25077/jrk.v13i1.437.

AutoDock. Available from: https://autodock.scripps.Edu. [Last accessed on 08 Nov 2022]

Pollastri MP. Overview on the rule of five. Curr Protoc Pharmacol. 2010;9:12. doi: 10.1002/0471141755.ph0912s49. PMID 22294375.

Radchenko VEV, Dyabina AS, Palyulin VA, Zefirov NS. Prediction of human intestinal absorption of drug compounds. Russ Chem Bull. 2016;65(2):576-80. doi: 10.1007/S11172-016-1340-0.

Pham The H, Cabrera Perez MA, Nam NH, Castillo Garit JA, Rasulev B, Le-Thi-Thu H. In silico assessment of ADME properties: advances in Caco-2 cell monolayer permeability modeling. Curr Top Med Chem. 2018;18(26):2209-29. doi: 10.2174/1568026619666181130140350, PMID 30499410.

Clark DE. In silico prediction of blood-brain barrier permeation. Drug Discov Today. 2003;8(20):927-33. doi: 10.1016/S1359-6446(03)02827-7.

Smith DA, Di L, Kerns EH. The effect of plasma protein binding on in vivo efficacy: misconceptions in drug discovery. Nat Rev Drug Discov. 2010;9(12):929-39. doi: 10.1038/NRD3287, PMID 21119731.

Bohnert T, Gan LS. Plasma protein binding: from discovery to development. J Pharm Sci. 2013;102(9):2953-94. doi: 10.1002/JPS.23614, PMID 23798314.

Blagg J. Structural alerts for toxicity. Burger’s medicinal chemistry and drug discovery. Published Online 2010:301-34. doi: 10.1002/0471266949. BMC128.

Limban C, Nuta DC, Chirita C, Negres S, Arsene AL, Goumenou M. The use of structural alerts to avoid the toxicity of pharmaceuticals. Toxicol Rep. 2018;5:943-53. doi: 10.1016/j.toxrep.2018.08.017, PMID 30258789. TOXREP.2018.08.017.