SCREENING DATABASE TANAMAN HERBAL INDONESIA SEBAGAI THYROID PEROXIDASE INHIBITOR PADA HIPERTIROIDISME DENGAN METODE MOLECULAR DOCKING

FAHRURROZI, KHARIZ (2017) SCREENING DATABASE TANAMAN HERBAL INDONESIA SEBAGAI THYROID PEROXIDASE INHIBITOR PADA HIPERTIROIDISME DENGAN METODE MOLECULAR DOCKING. Other thesis, Universitas Sebelas Maret.

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    Abstract

    Latar Belakang: Thyroid peroxidase (TPO) adalah enzim yang berperan penting dalam oksidasi iodida menjadi iodin pada pembentukan hormon tiroid. Enzim ini merupakan target obat anti-tiroid seperti methimazole (MMI) dan propylthiouracil (PTU). Walaupun sering digunakan sebagai first line drug pada hipertiroidisme, obat tersebut memiliki efek samping seperti agranulositosis dan hepatitis. Sampai sekarang belum ada alternatif obat yang lebih aman. Di sisi lain, Indonesia memiliki banyak tanaman herbal yang diketahui memiliki efek terapeutik. Penelitian ini bertujuan untuk menapis senyawa tanaman herbal Indonesia sebagai TPO inhibitor dengan metode molecular docking. Metode Penelitian: Total sampling digunakan untuk memperoleh sampel dari database HerbalDB dan PubChem berdasarkan kriteria Lipinski’s rule of five. Struktur TPO manusia didapatkan melalui modeling menggunakan SWISS-MODEL dengan template Bovine Lactoperoxidase (PDB ID 4gm7). Docking antara model TPO dan senyawa herbal dilakukan menggunakan Autodock Vina 1.1.2 dan divisualisasikan menggunakan Pymol 1.8. Energi dan lokasi ikatan senyawa herbal kemudian dibandingkan dengan standar (MMI). Senyawa dengan energi ikatan lebih rendah serta yang memiliki ikatan mirip MMI dipilih sebagai kandidat TPO inhibitor. Hasil Penelitian: Model TPO manusia didapatkan dengan kesamaan sequence sebesar 48,24%. Dari 457 senyawa herbal, 58 diantaranya memiliki ikatan mirip MMI pada residu Asp238 dan memiliki energi ikatan kurang dari -4,0 kkal/mol. Sepuluh kandidat TPO inhibitor berdasarkan energi ikatan yang terbentuk (dalam kkal/mol) diantaranya adalah Boeravinone F (-9,7), L(+) Tartaric acid (-9,64), Baicalein (-9,48), Vitexilactone (-9,34), Pedunculin (-8,86), Voacristine (-8,8), Tubotaiwin (-8,78), Ellagic Acid (-8,68), Gibberellin A5 (-8,68), dan Sweroside (-8,62). Dari sepuluh senyawa tersebut L(+) Tartaric acid memiliki konformasi, jumlah hidrogen donor, dan akseptor yang mirip MMI serta bersifat lebih lipofilik sehingga kemungkinan senyawa ini lebih poten dibandingkan MMI. Simpulan: L(+) Tartaric acid secara in silico berpotensi sebagai TPO inhibitor. Kedepannya penelitian dengan metode flexible docking diperlukan untuk memvalidasi hasil penelitian ini dan penelitian in vitro diperlukan untuk menguji aktivitas senyawa tersebut terhadap TPO. Kata kunci: thyroid peroxidase, hipertiroidisme, molecular docking, senyawa herbal --- Background: Thyroid peroxidase (TPO) plays an important role in the oxidation of iodide to iodine for thyroid hormone synthesis. TPO is the main target of anti-thyroid drugs such as methimazole (MMI) and propylthiouracil (PTU). Although these drugs are frequently used as the first line drugs for hyperthyroidism, they possess some adverse effects such as agranulocytosis and hepatitis. So far, there are no safer alternative drugs available. On the other hand, Indonesia has many herbal compounds known to have therapeutic effects. This research study is aimed to screen Indonesian herbal compounds as TPO inhibitor using the molecular docking technique. Methods: Total sampling was used to obtain samples from HerbalDB and PubChem database according to Lipinski’s rule of five. Human TPO structure was modeled using SWISS-MODEL based on Bovine Lactoperoxidase template (PDB ID 4gm7). All compounds were docked against TPO model using Autodock Vina 1.1.2 and visualized using Pymol 1.8. Their binding affinity and location then compared to the standard compound (MMI). Compounds having lower affinity and similar bond to MMI were chosen as TPO inhibitor candidates. Results: TPO model were obtained with 48,24% sequence identity. Docking and visualization of 457 unique compounds results in 58 compounds having similar bond to MMI at Asp238 and posses binding affinity less than -4,0 kcal/mol. Ten TPO inhibitor candidates based on their binding affinity (in kcal/mol) were Boeravinone F (-9,7), L(+) Tartaric acid (-9,64), Baicalein (-9,48), Vitexilactone (-9,34), Pedunculin (-8,86), Voacristine (-8,8), Tubotaiwin (-8,78), Ellagic Acid (-8,68), Gibberellin A5 (-8,68), and Sweroside (-8,62). Of those ten compounds, L(+) Tartaric acid shares close similarity to MMI in it’s conformation, hydrogen acceptor and donor. This compound is also more lipophilic. These properties might indicate that this compound has more potential than MMI. Conclusion: L(+) Tartaric acid is a potential TPO inhibitor in silico. Future studies using flexible docking technique are required to validate this result and in vitro studies are needed to evaluate these compounds activity against TPO. Keywords: thyroid peroxidase, hipertiroidism, molecular docking, herbal compound

    Item Type: Thesis (Other)
    Subjects: R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine
    Divisions: Fakultas Kedokteran
    Fakultas Kedokteran > Pendidikan Kedokteran
    Depositing User: Retno Andriani
    Date Deposited: 24 Mar 2017 12:22
    Last Modified: 24 Mar 2017 12:22
    URI: https://eprints.uns.ac.id/id/eprint/32258

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