Analisis In Silico Senyawa Bioaktif Biji Jintan Hitam sebagai Inhibitor Angiotensin-I Converting Enzyme (ACE)

Abstract

ACE merupakan salah satu reseptor utama dalam regulasi tekanan darah serta paling umum dihambat untuk mengatasi hipertensi. Biji jintan hitam dipercaya memiliki banyak manfaat, salah satunya menurunkan tekanan darah. Penelitian ini bertujuan mengidentifikasi interaksi molekuler serta menyeleksi dan memprediksi potensi inhibisi senyawa bioaktif biji jintan hitam terhadap ACE sebagai obat antihipertensi. Penelitian dilakukan dengan penapisan virtual 97 ligan uji menggunakan PyRx Virtual Screening Tool dan penambatan molekuler menggunakan AutoDock Tools. Hasil analisis interaksi ligan-reseptor menunjukkan 14 dari 20 ligan yang diuji pada tahapan tersebut memiliki potensi sebagai inhibitor ACE. Epicatechin menjadi ligan dengan potensi terbaik (ΔG -7.00 kkal/mol; BSS 62.50%) serta memenuhi pendekatan keberadaan interaksi terhadap Zn. Meskipun tidak menjadi ligan terbaik, terdapat tiga senyawa khas biji jintan hitam yang diidentifikasi juga berpotensi sebagai inhibitor ACE, yaitu trans-4-methoxy-thujane (ΔG -5.20 kkal/mol; BSS 68.75%) yang memenuhi pendekatan keberadaan interaksi terhadap Zn serta thymoquinone (ΔG -5.50 kkal/mol; BSS 43.75%) dan thymohydroquinone (ΔG -5.20 kkal/mol; BSS 50.00%) yang memenuhi pendekatan keberadaan ikatan hidrogen pada sisi aktif.

ACE is one of the main receptors in the regulation of blood pressure and is the most commonly inhibited to treat hypertension. Black cumin seeds are believed to have many benefits, one of them is lowering blood pressure. This study aims to identify molecular interactions as well as to select and predict the ACE inhibition potential of bioactive compounds from black cumin seeds as an antihypertensive drug. The research began with virtual screening of 97 ligands using the PyRx Virtual Screening Tool and molecular docking using AutoDock Tools. The results of the ligand-receptor interaction analysis showed that 14 of the 20 ligands tested at that step had potential as ACE inhibitors. Epicatechin became the ligand with the best potency (ΔG -7.00 kcal/mol; BSS 62.50%) and qualify to the approach of the presence of an interaction with Zn. Although not the best ligand, there are three unique ligands of black cumin seeds that were identified as potential ACE inhibitors, those are trans-4-methoxy-thujane (ΔG -5.20 kcal/mol; BSS 68.75%) which qualify to the approach of the presence of an interaction with Zn, also thymoquinone (ΔG -5.50 kcal/mol; BSS 43.75%) and thymohydroquinone (ΔG -5.20 kcal/mol; BSS 50.00%) which qualify the approach of the presence of hydrogen bonds on the active site.