Studi Network Pharmacology dan Molecular Docking Senyawa Golongan Flavonoid Daun Gagatan Harimau (Ampelocissus thyrsiflora (Blume) Planch) pada Kanker Payudara

Abstract

Background: Triple negative breast cancer is the most aggressive type of breast cancer. Most experience recurrence within 1 to 2 years and only about 30% of patients have a survival rate of more than 5 years. Tiger Crow is an endemic Sumatran plant that has been widely used in traditional medicine due to its high antioxidant content. Objective: This study aims to determine the target protein of tiger gagatan leaf flavonoid compounds that play a role in triple negative breast cancer and to determine tiger gagatan leaf flavonoid compounds that meet the physicochemical parameters, pharmacokinetics and can be the main target protein inhibitor in triple negative breast cancer regulation as one of the candidate anti-cancer compounds in silico. Method: The research was conducted through network pharmacology, molecular tethering to target proteins and prediction of pharmacokinetics and physicochemistry using SwissADME. Results: Based on the results of Network pharmacology obtained 2 target proteins namely Akt1 and Src which are the main proteins in the regulation of triple negative breast cancer. From the results of molecular tethering on Akt1, the grid score ranges from -38.711124 to -71.387894 and on the Src receptor, the grid score ranges from -40.337402 to -65.824432. There are similarities in bonds and amino acid residues between the Akt1 binding pocket and 5 flavonoid compounds of tiger gagatan leaves, namely kaempferol, mearnsitrin, myricetin, isorhamnetin and isorhamnetin 3-o-rhamnoside and in Src receptors there are 4 compounds that have similar amino acid residues with the binding pocket, namely kaempferol, mearnsitrin, myricetin, and isorhamnetin 3-o-rhamnoside. Based on the prediction of physicochemical properties, 4 compounds namely kuersetin, kaempferol, myricetin and isorhamnetin meet the requirements of Lipinski's Rule of Five and the compounds kuersetin, kaempferol, isorhamnetin have a high gastrointesitinal absorption pharmacokinetic profile, exclude the Blood Brain Barrier, good skin permeability, are not P- glycoprotein substrates and do not inhibit most major CYP enzymes. Conclusion: Akt1 and Src proteins are predicted to be the main proteins in the regulation of triple negative breast cancer. From the results of molecular tethering, there are 5 compounds that are predicted to have inhibitory activity on the Akt1 receptor and as many as 4 compounds have inhibitory activity on the Src receptor. Based on the prediction of physicochemical and pharmacokinetic properties, 4 flavonoid compounds of tiger crow leaf are predicted to meet the physicochemical and pharmacokinetic parameters.