Molecular Docking of The Potential Compound from Cocoa Shells (Theobroma cacao L.) Against Androgen Receptor as Anti-Alopecia

Resmi Mustarichie


The determination of the components of the cocoa shells compounds that have anti-alopecia activity have not been reported, so the molecular docking approach is a very effective alternative before further testing is carried out. This study aimed to determine the potential compound components against androgen receptor targets as anti-alopecia drugs. Molecular docking used ChemDraw Ultra 12.0, Chem3D Pro 12.0, Biovia Discovery Studio 2016 Client®, and Autodock Tools 4.2, as well as to determine the pharmacokinetic properties and toxicity of drug ingredients with Pre-ADMET. It was found that that the components of the cocoa peel compound had the potential to act as anti-alopecia drugs, namely chlorogenic acid, epicatechin, and catechins with the value of the free energy binding (ΔG) and the inhibition constant (Ki) respectively (-7.87 kcal/mol; 1.70 µM)> (-6.48 kcal/mol; 17.65 µM)> (-6.36 kcal/mol; 21.91 µM) with the crucial amino acid residue formed was GLN 858. The pharmacokinetics (plasma protein binding) of epicatechin and catechin were excellent compared to chlorogenic acid and minoxidil because it could penetrate the plasma membrane when interacting. While the toxicity test, the components of chlorogenic acid, epicatechin, and catechin compounds were mutagenic, and only chlorogenic acid was carcinogenic. The study concluded chlorogenic acid, epicatechin, and catechin compounds from the cocoa shells were promising candidates for anti-alopecia drugs to be developed further targeting androgen receptors. It was consistent with the molecular docking results, which showed that ΔG and Ki's values were excellent compared to minoxidil. The pre-ADMET results also showed that the epicatechin and catechin compounds components could penetrate the plasma membrane when given topically compared to minoxidil.
Keywords: Alopecia, Cocoa shells, Theobroma cacao, Molecular docking, Androgen receptor.

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Kaushik R, Gupta D, Yadav R (2014) Alopecia : Herbal Remedies. Int. J. Pharm. Sci. Res., 2(7):1631-7.

Hsu CL, Liu JS, Lin AC, Yang CH, Chung WH, Wu WG (2014) Minoxidil may suppress androgen receptor-related functions, Oncotarget, 5(8):2187-97. doi: 10.18632/oncotarget.1886.

Triyangkulsri K, Srisuwanwattana P, Sriphojanart T, Suchonwanit P (2019) Fibrosing Alopecia in a Pattern Distribution: A Case Report and Literature Review, Case Reports in Dermatology, 01 Sep 11(3):297-302. DOI: 10.1159/000503681

Mustarichie R, Hasanah AN (2019) Anti-alopecia activity of waste cacao (Theobroma cacao L .) shells. Drug Invent Today, 11(9):7-12.

Stela Jokic S, Gagic T, Knez Z, Šubaric D, Škerget M (2018) Separation of Active Compounds from Food by-Product (Cocoa Shell) Using Subcritical Water Extraction, Molecules, 23: 1408. doi:10.3390/molecules23061408

Ördög R, Grolmusz V (2008) Evaluating Genetic Algorithms in Protein-Ligand Docking, Conference: Bioinformatics Research and Applications, Fourth International Symposium, ISBRA 2008, Atlanta, GA, USA, May 6-9. Proceedings. DOI: 10.1007/978-3-540-79450-9_37.

Kim R, Skolnick J (2008) Assessment of Programs for Ligand Binding Affinity Prediction, J Comput Chem., 29(8):1316-31. doi: 10.1002/jcc.20893

Cole JC, Murray CW, Nissink JWM, Taylor RD, Taylor R (2005) Comparing protein-ligand docking programs is difficult, Proteins Struct. Funct. Genet., 60(3):325-32.

Muttaqin FZ (2019) Molecular Docking and Molecular Dynamic Studies of Stilbine Derivate Compounds as Sirtuin-3 (SIRT3) Histone Deacetylase Inhibitor on Melanoma Skin Cancer and Their Toxicities. J. Pharmacop., 2(2):112-21.

Kolina J, Sumiwi SA, Levita J (2018) Mode Ikatan Metabolit Sekunder di Tanaman Akar Kuning (Arcangelisia flava L.) dengan Nitrat Oksida Sintase. Fitofarmaka J Ilm Farm., 8(1):50-8. DOI:10.33751/JF.V8I1.1171

Forli S, Huey R, Pique ME, Sanner MF, Goodsell DS, Olson AJ (2016) Computational protein-ligand docking and virtual drug screening with the AutoDock suite. Nat. Protoc., 11(5):905-119.

Drie JH (2005) Pharmacophore-based virtual screening: A practical perspective. In J. Alvarez dan B. Shoichet. Virtual Screening in Drug Discovery. Florida-USA: CRC Press.

Yanuar A (2012) Penambatan Molekular Praktek dan Aplikasi Pada Virtual Screening. Indonesia: Penerbit Fakultas Farmasi Universitas Indonesia. Depok;.

Roy D, Kumar V, Acharya KK (2014) Probing the Binding of Syzygium-Derived α-Glucosidase Inhibitors with N- and C-Terminal Human Maltase Glucoamylase by Docking and Molecular Dynamics Simulation. Appl Biochem Biotechnol., 102-114.

Bissantz C, Folkers G, Rognan D (2000) Protein-Based Virtual Screening of Chemical Databases. 1. Evaluation of Different Docking / Scoring Combinations, 4759-67.

Kontoyianni M, Mcclellan LM, Sokol GS (2004) Evaluation of Docking Performance : Comparative Data on Docking Algorithms, 558-65.

Pratama MRF (2015) Molecular Docking of Anticancer Agents: Artemisinin and Derivates as HER2 Inhibitor. Proceedings of 1st Sari Mulia International Conference on Health and Science, 2015: 1-12.

Pangastuti A, Amjn M, Indriwati ES (2016) Mengungkap Potensi Senyawa Alami Melalui Teknik Reverse Docking. Pros Semin Nas II 2016, Kerjasama Prodi Pendidik Biol FKIP dengan Pus Stud Lingkung dan Kependud Univ Muhammadiya Malang., (1):1019-28.

Umamaheswari M, Madeswaran A, Asokkumar K (2013) Virtual Screening Analysis and In-vitro Xanthine Oxidase Inhibitory Activity of Some Commercially Available Flavonoids. Iran J. Pharm. Res IJPR., 12(3):317-23.

Kelutur FJ, Mustarichie R, Umar AK (2020) Virtual Screening Kandungan Senyawa Kipas Laut (Gorgonia mariae) sebagai Antiasma. J. Penelit Kim., 16(2):199-210.

Megantara S, Levita J, Iwo MI, Ibrahim S (2018) Absorption, distribution and toxicity prediction of andrographolide and its derivatives as anti-HIV drugs. Res J. Chem. Environ., 22(1):82-5.

NursamsiarN, Toding AT, Awaluddin A (2016) Studi In Silico Senyawa Turunan Analog Kalkon dan Pirimidin sebagai Antiinflamasi: Prediksi Absorpsi, Distribusi, dan Toksisitas. J. Pharmacy, 13(1):92-100.


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