Virtual Screening Kandungan Senyawa Kipas Laut (Gorgonia mariae) sebagai Antiasma

Faruk Jayanto Kelutur, Resmi Mustarichie, Abdul Kakhar Umar

Abstract

Kipas laut (Gorgonia mariae) telah digunakan masyarakat Maluku secara turun temurun sebagai obat asma. Kandungan metabolit sekunder yang paling dominan dalam kipas laut adalah sterol, dimana memiliki aktivitas terapi melalui efek sinergisme antara senyawa metabolit dengan polivalent activity. Pengujian kipas laut sebagai anti-asma belum pernah dilaporkan sebelumnya. Oleh karena itu, perlu dilakukan virtual screening menggunakan metode in silico pada komponen sterol kipas laut sebagai tahap awal dalam menentukan efektivitas terapi anti-asma dengan memprediksi nilai ikatan energi bebas (ΔG), konstanta inhibisi (Ki), dan interaksi residu asam amino menggunakan Autodock Tools 4.2 dan Discovery Studio 2016 Client®. Keamanan dan efektivitas kandidat obat dievaluasi menggunakan parameter dari Lipinski Rule of Five dan pre-ADMET. Hasil penelitian menunjukkan bahwa konstanta inhibisi dan ikatan energi bebas (Ki; ΔG) dari komponen senyawa kipas laut dapat diurutkan secara potensial yaitu 4,24-dimetil kolestanol  (0,809; -12,40) > 24-metil-22-dehidrokolesterol (0,864; -12,36) > 23-demetil gorgosterol (1,74; -11,95) > 4,24-dimetil-22-dehidrokolestanol (1,89; -11,90). Residu asam amino yang berperan penting dalam aktivitas inhibisi hCHIT1 adalah 213-ASP. Semua komponen senyawa uji memiliki nilai log P lebih dari 5 yang menunjukkan bahwa kelarutan dan toksisitas perlu diperhatikan. Evaluasi distribusi pre-ADMET berdasarkan nilai dari pengikatan protein plasma menunjukan bahwa senyawa uji dapat berdifusi menembus membran plasma dan berinteraksi sesuai target farmakologi. Selain itu, hasil parameter uji toksisitas menunjukkan bahwa senyawa 23-demetil gorgosterol dan 4,24-dimetil-22-dehidrokolestanol memiliki potensi sebagai anti-asma.

Virtual Screening of the Compounds in Gorgonians (Gorgonia mariae) as anti-asthma. The people of Maluku have used Kipas laut (G. mariae) for generations as an asthma medicine. The secondary metabolite that is most dominant in kipas laut is sterols, which have therapeutic activity through the synergistic effect between metabolite compounds and polyvalent activity. Anti-asthma activity of kipas laut has never been reported. Therefore, it is necessary to do virtual screening using the in silico method on the sterol component of kipas laut as a first step in determining the effectiveness of anti-asthma therapy by predicting the value of free energy bonds (ΔG), constant inhibition (Ki), and interactions of amino acid residues using Autodock Tools 4.2 and Discovery Studio 2016 Client®. The effectiveness and safety of prospective drugs are evaluated using the Lipinski Rule of Five and pre-ADMET. The results showed that the value of inhibition constants and free energy bonds (Ki; ΔG) on the compound of kipas laut that was potentially sorted was 4.24-dimethyl cholestanol (0.809; -12.40) > 24-methyl-22-dehydrocholesterol (0.864; -12.36) > 23-demethyl gorgosterol (1.74; -11.95) > 4.24-dimethyl-22-dehidrokolestanol (1.89; -11.90). The crucial residues of amino acids is 213-ASP, which play a significant role in hCHIT1 inhibitory activity. All components of the test compound have a log P value of more than five, which indicates that solubility and toxicity need to be considered. Evaluation of the pre-ADMET based on the value of plasma protein binding shows that the test compound can diffuse through the plasma membrane and interact according to pharmacological targets. In addition, the results of the toxicity test showed that 23-demethyl gorgosterol and 4.24-dimethyl-22-dehidrokolestanol compounds have potential as anti-asthma.

Keywords

Anti-asthma; in silico; kipas laut (G. marie); sterol

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DOI: https://doi.org/10.20961/alchemy.16.2.39965.199-210

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