ANALYSIS OF PHARMACOKINETICS, TOXICITY AND DRUG-LIKENESS OF FIVE ARECA NUTS COMPOUNDS AS ANTIDEPRESSANTS IN SILICO
Keywords:
ADME, antidepressant, areca nut, drug-likeness, toxicity
Abstract
This study aims to screen the potential of five active compounds in areca nut L-phenylalanine, protocatechuic acid, ocanine, nicotinic acid, L-tyrosine as antidepressants through pharmacokinetic analysis and drug likeness analysis using the SwissADME online application, then predict toxicity and brain penetration through 2D radar bioavailability results. using the ADMETLab online application. Compounds that met all parameters were L-phenylalanine and L-tyrosine with high GI absorption results, no P-gp inhibitors, no CYP1A2 inhibitors, no CYP2D6 inhibitors, yes BBB permeant and had a logKp value <2.5cm/s, no hepatotoxicity and no AMES toxicity, complies with Lipinski, Ghose, Veber regulations, bioavailability score 0.55, and showed the optimal range of values as an oral drug.
References
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[22] Aufa, W., Surya, A. dan Nurul, M. (2018). Uji Toksisitas Sub Akut Infusa Daun Afrika (Vernonina amygdalina Del.) terhadap Histopatologi Ginjal Mencit Galur BALB/C. Pharm. J. Islam. Pharm., 2(1). 1–9.
[23] Kesuma, D., Siswandono, S., Purwanto, B. dan Hardjono, S. (2018). Uji in silico Aktivitas Sitotoksik dan Toksisitas Senyawa Turunan N-(Benzoil)-N’- feniltiourea Sebagai Calon Obat Antikanker. J. Pharm. Sci. Clin. Res., 1. 1–11.
[24] Ananta, K. D. dan Santoso, B. (2018). Kajian Ikatan 3D Molekuler Senyawa Terpilih Ketumbar (Coriandrum sativum) dan Adas Bintang (Anisi Stellati) terhadap sintase 6 , 7-dimetil-8-ribitillumazin (2VI5 , 2C92) Mycobacterium tuberculosis. J. STIKES, 7.320–327.
[25] Jusnita, N. dan Syurya, W. (2019). Karakterisasi Nanoemulsi Ekstrak Daun Kelor (Moringa oleifera Lamk.). J. Sains Farm. Klin., 6(1).16–24.
[26] Nambiar, M. P. dan Biju, A. R. (2022). Designing of promising Tromethamine-Diflunisal-Pyrrole combinations based on COX binding, drug-properties and safety. Indian J. Biochem. Biophys., 59(7). 732–740.
[27] Narko, T., Permana, B., Prasetiawati, R., Soni, D. dan Khairiyah, F. (2017). Molecular docking study of bulb of bawang dayak (Eleutherine palmifolia (L) Merr) compound as anti servical cancer. J. Ilm. Farm. Bahari, 8(2).1–14.
[28] Daina, A., Michielin, O. dan Zoete, V. (2017). SwissADME: A Free Web Tool to Evaluate Pharmacokinetics, Drug-likeness and Medicinal Chemistry Friendliness of Small Molecules. Sci. Rep., 7(42717)1–13.
[2] Sari, O. (2019). Determinan Kejadian Keguguran di Indonesia Tahun 2014 (Analisis Data Sekunder Indonesia Family Life Survey). Skripsi. Universitas Sriwijaya.
[3] Ridlo, I. A. (2020). Pandemi COVID-19 dan Tantangan Kebijakan Kesehatan Mental di Indonesia. Insan J. Psikologi dan Kesehatan Mental, 5(2). 155–164.
[4] Wilar, G., Indriyati, W., dan Subarnas, A. (2014). Pemanfaatan Dan Pengolahan Limbah Kulit Pisang Menjadi Permen Kulit Pisang yang Berkhasiat Antidepresi Dalam Upaya Pemberdayaan Kesehatan Dan Perekonomian Masyarakat Desa Di Kecamatan Karang Tengah Kabupaten Cianjur. J. Apl. Ipteks untuk Masy., 3(1). 5–8.
[5] Naoi, M., Maruyama, W., dan Shamoto-Nagai, M. (2017). Type A Monoamine Oxidase and Serotonin are Coordinately Involved in Depressive Disorders: from Neurotransmitter Imbalance to Impaired Neurogenesis. J. Neural Transm., 125(1). 53–66.
[6] Youdim, M. B. H., Edmondson, D, dan Tipton, K. F. (2006). The therapeutic potential of monoamine oxidase inhibitors. Nat. Rev. Neurosci., 7(4). 295–309.
[7] Kaludercic, N., Mialet-Perez, J., Paolocci, N., Parini, A. dan Lisa, F. (2014). Monoamine oxidases as sources of oxidants in the heart. J. Mol. Cell. Cardiol., 1(1). 1–9.
[8] Abbas, G., Naqvi, S., Erum, S., Ahmed, S., Atta-Ur-Rahman, dan Dar, A. (2012). Potential antidepressant activity of areca catechu nut via elevation of serotonin and noradrenaline in the hippocampus of rats. Phyther. Res., 27(1). 39–45.
[9] Peng, W., Liu, Y., Zhao, C., Huang, X., Wu, N., Hu, M., Xie, D. dan Wu, C. (2015). In Silico Assessment of Drug-like Properties of Alkaloids from Areca Catechu L nut. 635-639.
[10] Adelina, R. (2013). Kajian Tanaman Obat Indonesia yang Berpotensi sebagai Antidepresan. J. Kefarmasian Indonesia, 3(1). 9–18, 2013.
[11] Rimon, R. (1993). Moclobemide versus imipramine in depressed out-patients: a double-blind multi-centre study. Int. Clin. Pharmacol., 7. 141–147.
[12] Dhingra, D dan Sharma, A. (2005). Evaluation of Antidepressant-like Acitivity of Glycyrrhizin in Mice. J. Med. Food, 9(1). 84–89.
[13] Dar, A., Khatoon, S., Rahman, G. dan Atta-Ur-Rahman. (1997). Anti-depressant activities of Areca catechu fruit extract. Phytomedicine, 4(1). 41–45.
[14] Boucher, B. J. dan Mannan, N. (2002). Metabolic effects of the consumption of Areca catechu. Addict. Biol., 7(1). 103–110.
[15] Wahyuni, A. A. S. (2017). Hubungan Genmonoamine Oxidase A (MAO A) dengan Agresivitas dan Perilaku Antisosial. Skripsi. Universitas Udayana.
[16] Novianty, R., Ananta, S. dan Karim, M. A. (2021). Herbal plants from Riau Province as inhibitors of COVID-19 binding to ACE2 receptor by computer aided molecular design an in-silico method. J. Phys. Conf. Ser., 1788(1). 1–8.
[17] Ananta, S. dan Novianty, R. (2022). Simulasi Dinamika Molekuler Senyawa Kompleks MAO-A dan Safrol sebagai Kandidat Antidepresan menggunakan Aplikasi Gromacs. Repos. Univ. Riau. 1–9.
[18] Maylinda, S. dan Novianty, R. (2022). Studi In Silico Senyawa Safrole sebagai Kandidat Antidepresan. Repos. Univ. Riau. 1–18.
[19] Ningsih, U. P. dan Novianty, R (2021). Studi In Silico Senyawa Arecoline (Areca catechu L.) sebagai Kandidat Antidepresan. Repos. Univ. Riau. 1–12.
[20] Sirait, V. V. dan Novianty, R. (2022). Analisis Studi In Silico Seyawa Guineensine sebagai Kandidat Obat Antidepresan. Repos. Univ. Riau.1–15.
[21] Yang, Y., Huang, H., Cui, Z., Chu, J. dan G. Du. (2021). UPLC–MS/MS and Network Pharmacology-Based Analysis of Bioactive Anti-Depression Compounds in Betel Nut. Drug Des. Devel. Ther., 15. 4827–4836.
[22] Aufa, W., Surya, A. dan Nurul, M. (2018). Uji Toksisitas Sub Akut Infusa Daun Afrika (Vernonina amygdalina Del.) terhadap Histopatologi Ginjal Mencit Galur BALB/C. Pharm. J. Islam. Pharm., 2(1). 1–9.
[23] Kesuma, D., Siswandono, S., Purwanto, B. dan Hardjono, S. (2018). Uji in silico Aktivitas Sitotoksik dan Toksisitas Senyawa Turunan N-(Benzoil)-N’- feniltiourea Sebagai Calon Obat Antikanker. J. Pharm. Sci. Clin. Res., 1. 1–11.
[24] Ananta, K. D. dan Santoso, B. (2018). Kajian Ikatan 3D Molekuler Senyawa Terpilih Ketumbar (Coriandrum sativum) dan Adas Bintang (Anisi Stellati) terhadap sintase 6 , 7-dimetil-8-ribitillumazin (2VI5 , 2C92) Mycobacterium tuberculosis. J. STIKES, 7.320–327.
[25] Jusnita, N. dan Syurya, W. (2019). Karakterisasi Nanoemulsi Ekstrak Daun Kelor (Moringa oleifera Lamk.). J. Sains Farm. Klin., 6(1).16–24.
[26] Nambiar, M. P. dan Biju, A. R. (2022). Designing of promising Tromethamine-Diflunisal-Pyrrole combinations based on COX binding, drug-properties and safety. Indian J. Biochem. Biophys., 59(7). 732–740.
[27] Narko, T., Permana, B., Prasetiawati, R., Soni, D. dan Khairiyah, F. (2017). Molecular docking study of bulb of bawang dayak (Eleutherine palmifolia (L) Merr) compound as anti servical cancer. J. Ilm. Farm. Bahari, 8(2).1–14.
[28] Daina, A., Michielin, O. dan Zoete, V. (2017). SwissADME: A Free Web Tool to Evaluate Pharmacokinetics, Drug-likeness and Medicinal Chemistry Friendliness of Small Molecules. Sci. Rep., 7(42717)1–13.
Published
2023-04-20
How to Cite
Novianty, R. (2023). ANALYSIS OF PHARMACOKINETICS, TOXICITY AND DRUG-LIKENESS OF FIVE ARECA NUTS COMPOUNDS AS ANTIDEPRESSANTS IN SILICO. Jurnal Inovasi Pendidikan Dan Sains, 4(1), 61-66. https://doi.org/10.51673/jips.v4i1.1511
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