Studi In Silico Aktivitas Senyawa Steroid Terhadap Antikanker Payudara Menggunakan Estrogen Alfa (ER-α)
Authors: Nurlelasari Nurlelasari , Widyana Almas , Julaeha Euis , Hardianto Ari , Huspa Desi Harneti Putri , Maharani Rani , Mayanti Tri , Darwati Darwati , Hanafi Muhammad , Supratman Unang 
Published: March 2023

<p><span lang="IN">Kanker payudara merupakan penyebab kedua terbanyak kematian pada wanita akibat kanker setelah kanker paru-paru di seluruh dunia. </span><span lang="IN">Steroid merupakan kelompok senyawa aktif yang diantaranya berhasil diisolasi dari genus <em>Chisocheton</em> yang dilaporkan memiliki aktivitas melawan sel kanker payudara MCF-7. Tujuan penelitian ini adalah untuk mengetahui interaksi senyawa steroid terhadap estrogen alfa (ER-</span><span>α</span><span lang="IN">) melalui metode <em>in silico</em>, yaitu penambatan molekul. Pemodelan struktur tiga dimensi (3D) senyawa steroid dilakukan dengan memperhatikan keadaan terprotonasinya pada pH 7,4. </span><span lang="IT">Metode <em>in silico</em> divalidasi melalui penambatan ulang struktur kristal ER-</span><span>α</span><span lang="IT">, hingga diperoleh </span><span lang="IT">nilai RMSD &lt; 2 Å, dengan program AutoDock 4.2.6. Dengan program yang sama, senyawa-senyawa steroid ditapis dengan metode penambatan molekul. Hasil penapisan menghasilkan nilai energi bebas dari kedua senyawa steroid yaitu -10,08 kkal/mol (7</span><span>α</span><span lang="IT">-hidroksi-</span><span>β</span><span lang="IT">-sitosterol) dan -10,75 kkal/mol (stigmast-5-en-3</span><span>β</span><span lang="IT">-ol), yang nilainya lebih baik dari estradiol (-9,62 kkal/mol), sebagai ligan alami ER-</span><span>α</span><span lang="IT">. Kedua senyawa ini berpotensi untuk menginhibisi estrogen alfa, dimana senyawa stigmast-5-en-3</span><span>β</span><span lang="IT">-ol memiliki potensi yang lebih besar karena nilai energi bebasnya lebih rendah. Hal ini menandakan bahwa m</span><span>odifikasi struktur senyawa mampu mengubah nilai energi ikatan dan interaksi antara ligan dan reseptor.</span></p><p><span><strong><span lang="EN-US">In Silico Study of Steroid Compound Activity Against Breast Cancer Using Estrogen Alpha (ER-α). </span></strong><span lang="EN-US">Breast cancer is the second worldwide leading cause of cancer death in women after lung cancer. Steroids are a group of active compounds isolated from the <em>Chisocheton</em> genus that has activity against MCF-7 breast cancer cells. This study aimed to determine the interaction activity of steroid compounds against alpha estrogen receptor (ER-α) through in silico method specifically mlecular docking. The modeling of the three-dimensional structure (3D) of steroid compounds was performed by considering their protonation states at pH 7.4. The in silico method was validated by redocking the crystal structure of ER-α until obtaining an RMSD value &lt; 2 Å, using the AutoDock 4.2.6 program. </span><span lang="EN-US">Steroids compounds were screened with the same program namely the molecular docking method. Screening results show that the free energy values of the steroid compounds were -10.08 kcal/mol (7α-hydroxy-β-sitosterol) and -10.75 kcal/mol (stigmast-5-en-3β-ol), which are stronger than estradiol (-9.62 kcal/mol) as native ligand of ER-α. Both of these compounds can inhibit the alpha estrogen receptor, in which the stigmast-5-en-3β-ol compound has a greater potential because of its lower free energy value. This finding indicates that modification of the compound's structure could change the binding energy value and interaction between ligands and receptors.</span></span></p>