Molecular Docking Study of Flavonoid Compounds in The Guava Leaves (Psidium Guajava L.) Which Has Potential as Anti-Inflammatory COX-2 Inhibitors
Authors: Ahsana Dina , Andika Andika , Nashihah Siti 
Published: January 2022

ABSTRAKInflamasi yang bersifat progresif cenderung akan merusak dan menimbulkan beberapa permasalahan dalam tubuh. Enzim COX-2 merupakan salah satu mediator yang berkontribusi besar dalam terjadinya inflamasi progresif. Penelitian secara eksperimental daun jambu biji (Psidium guajava L.) terbukti memiliki aktivitas anti-inflamasi diduga karena banyak terkandung senyawa flavonoid, namun masih belum ada penelitian aktivitasnya terhadap penghambatan COX-2 selektif. Tujuan dari penelitian ini yaitu untuk mengetahui potensi senyawa flavonoid memiliki aktivitas anti-inflamasi penghambat COX-2 selektif menggunakan uji penambatan molekul. Metode: 31 senyawa flavonoid daun jambu biji didapat dari studi literatur beberapa penelitian in-vitro dan kode protein ID: 6COX yang digunakan pada penelitian penambatan molekular ini dilakukan energi minimisasi terlebih dahulu. Selanjutnya digunakan software docking Autodock4 dengan metode semi-flexible dan Lamarckian Genetic Algorithm (LGA). Semua senyawa flavonoid juga dilakukan prediksi Absorpsi, Distribusi, Metabolisme, Ekskresi, Toksisitas (ADMET). Hasil: secara keseluruhan diperoleh semua 31 senyawa uji flavonoid daun jambu biji berpotensi sebagai inhibitor COX-2 dan beberapa senyawa uji diantaranya memiliki nilai docking ∆G terbaik yang berasal dari Epicatechin-3-O-Gallate sebesar -9,31 kcal/mol, disusul oleh Gallocatechin sebesar -8,97 kcal/mol serta Tamarixetin -8,83 kcal/mol. Residu asam amino SER 353, TYR 385, SER 530, GLN 192 dan ARG 120 juga banyak berkontibusi dalam terbentuknya ikatan hidrogen. Kesimpulan: Epicatechin-3-O-Gallate merupakan senyawa uji yang memiliki potensi besar sebagai anti-inflamasi inhibitor COX-2 selektif karena memiliki kekuatan dan kestabilan ikatan yang tinggi dengan energi docking terendah saat ditambatkan pada protein target. Kata kunci: Penambatan Molekuler; Autodock4; Psidium guajava L; Antiinflamasi Inhibitor ; COX-2; Flavonoid.ABSTRACTProgressive inflammation tends to damage and cause several problems in the body. The COX-2 enzyme is one of the mediators that have a significant contribution to progressive inflammation. Experimental study, guava leaves (Psidium guajava L.), have anti-inflammatory activity, presumably because they contain many flavonoid compounds. However, the lack of those research on their action against selective COX-2 inhibition. The purpose of this study is to determine the potential for flavonoid compounds to have anti-inflammatory activity of selective COX-2 inhibitors using molecular docking. Method: 31 flavonoids compound of guava leaves found on some literature studies of a systematic literature review and protein code ID: 6COX used on this molecular docking study by applying minimization energy at first. Next, using Autodock4 docking software with semi-flexible and Lamarckian Genetic Algorithm (LGA) methods. All flavonoid compounds also used screening Absorption, Distribution, Metabolism, Excretion, Toxicity (ADMET) prediction. Results: Overall results obtained that all 31 compounds of guava leaf flavonoids can potentially be COX-2 inhibitors. One of them has the best docking value with ∆G from Epicatechin-3-O-Gallate of -9.31 kcal/mol is high than the Gallocatechin of -8.97 kcal/mol and -8.83 kcal/mol Tamarixetin. The amino acid residues SER 353, TYR 385, SER 530, GLN 192, and ARG 120 contributed significantly to form hydrogen bonds. Conclusions: Epicatechin-3-O-Gallate has significant potential as an anti-inflammatory selective COX-2 inhibitor because it has high bond strength and stability with the lowest energy binding when attached to the target protein.Keyword: Molecular Docking; Autodock4; Psidium guajava L; Inhibitor Anti-inflammatory; COX-2; Flavonoids.