In Silico Molecular Docking and ADMET Analysis for Drug Development of Phytoestrogens Compound with Its Evaluation of Neurodegenerative Diseases

Faisal Akhmal Muslikh (1) , Reyhan Rahma Samudra (2) , Burhan Ma’arif (3) , Zulvikar Syambani Ulhaq (4) , Suko Hardjono (5) , Mangestuti Agil (6)
(1) Universitas Airlangga , Indonesia
(2) Universitas Islam Negeri Maulana Malik Ibrahim Malang , Indonesia
(3) Universitas Islam Negeri Maulana Malik Ibrahim Malang , Indonesia
(4) National Research and Innovation Agency Republic of Indonesia , Indonesia
(5) Universitas Airlangga , Indonesia
(6) Universitas Airlangga , Indonesia

Abstract

Neurodegenerative disease is one of the problems faced by postmenopausal women due to estrogen deficiency. Phytoestrogen compounds can be used as an alternative treatment for diseases caused by estrogen deficiency by binding to their receptors through the estrogen receptor (ER) dependent pathway. With in silico studies, this study aims to predict how phytoestrogen compounds will stop neurons from dying by using the dependent ER pathway. Genistein, daidzein, glycitein, formononetin, biochanin A, equol, pinoresinol, 4-methoxypinoresinol, eudesmin, α-amyrin, and β-amyrin compounds were prepared with ChemDraw Ultra 12.0. Then their pharmacokinetic and pharmacodynamic properties were examined using SwissADME. Geometry optimization of the compound was performed using Avogadro 1.0.1, and molecular docking of the compound to the ERα (1A52) and ERβ (5TOA) receptors was performed using AutoDock vina (PyRx 0.8). The interaction visualization stage was carried out with Biovia Discover Studio 2021, while the toxicity values of the compounds were analyzed using pkCSM and ProTox II. The results showed that the equol compound met the pharmacokinetic, pharmacodynamic, toxicity criteria, and had similarities with the native ligand 17β-estradiol. Equol compound inhibits neurodegeneration via an ER-dependent pathway by binding to ERα (1A52) and ERβ (5TOA) receptors.

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Authors

Faisal Akhmal Muslikh
Reyhan Rahma Samudra
Burhan Ma’arif
Zulvikar Syambani Ulhaq
Suko Hardjono
Mangestuti Agil
mmangestuti@yahoo.com (Primary Contact)
Author Biographies

Faisal Akhmal Muslikh, Universitas Airlangga

Master Student of Pharmaceutical Science, Universitas Airlangga, Surabaya, East Java, Indonesia

Reyhan Rahma Samudra, Universitas Islam Negeri Maulana Malik Ibrahim Malang

Department of Pharmacy, Universitas Islam Negeri Maulana Malik Ibrahim Malang, Malang, East Java, Indonesia

Burhan Ma’arif, Universitas Islam Negeri Maulana Malik Ibrahim Malang

Department of Pharmacy, Universitas Islam Negeri Maulana Malik Ibrahim Malang, Malang, East Java, Indonesia

Zulvikar Syambani Ulhaq, National Research and Innovation Agency Republic of Indonesia

Research Center for Pre-Clinical and Clinical Medicine, National Research and Innovation Agency Republic of Indonesia, Cibinong, West Java, Indonesia

Suko Hardjono, Universitas Airlangga

Department of Pharmaceutical Science, Universitas Airlangga, Surabaya, East Java, Indonesia

Mangestuti Agil, Universitas Airlangga

Department of Pharmaceutical Science, Universitas Airlangga, Surabaya, East Java, Indonesia

1.
Muslikh FA, Samudra RR, Ma’arif B, Ulhaq ZS, Hardjono S, Agil M. In Silico Molecular Docking and ADMET Analysis for Drug Development of Phytoestrogens Compound with Its Evaluation of Neurodegenerative Diseases. Borneo J Pharm [Internet]. 2022Nov.30 [cited 2023Jan.30];5(4):357-66. Available from: https://journal.umpr.ac.id/index.php/bjop/article/view/3801

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