Studi Potensi Senyawa Golongan Flavonoid Daun Gagatan Harimau (Ampelocissus thyrsiflora (Blume) Planch) terhadap CHK2 dan WEE1 secara In Silico

Abstract

Background: Lung cancer is one of the leading causes of death worldwide, with a low survival rate due to late diagnosis. CHK2 and WEE1 are two proteins involved in cell cycle regulation, and their inhibition has the potential to enhance cancer therapy effectiveness. Flavonoid compounds from the leaves of Gagatan Harimau (Ampelocissus thyrsiflora (Blume) Planch) are known for their antioxidant and anticancer properties, making them potential candidates for anticancer drugs. Objective: This study aims to explore the potential of flavonoid compounds from Gagatan Harimau leaves in inhibiting CHK2 and WEE1 through in silico analysis, as well as evaluate their pharmacokinetics and toxicity parameters. Methods: This study was conducted using an in silico approach with the molecular docking method. Biological activity prediction was performed using PASS Online, physicochemical properties were evaluated using Lipinski’s Rule of Five, while pharmacokinetics and toxicity assessments were conducted using pkCSM and Protox-II. Molecular docking was carried out using DOCK6 software to analyze flavonoid interactions with CHK2 (PDB ID: 2YIQ) and WEE1 (PDB ID: 5VC5). Results: The biological activity prediction results showed that flavonoids from Gagatan Harimau leaves have Pa values > 0.7, indicating a high potential as drug candidates. Physicochemical evaluation revealed that kaempferol and isorhamnetin met the required criteria. Molecular docking results demonstrated that several flavonoid compounds exhibited strong binding affinities to CHK2 and WEE1, with competitive grid scores compared to reference inhibitors (PHI-101 and adavosertib). Pharmacokinetic evaluation indicated that all compounds met the parameters except for log BBB, while toxicity predictions classified most flavonoids as safe. Conclusion: Flavonoid compounds from Gagatan Harimau leaves show potential as anticancer drug candidates capable of inhibiting CHK2 and WEE1 through in silico analysis. Further in vitro and in vivo studies are required to validate their effectiveness and safety for lung cancer therapy.