In Silico Analysis of Selective Bioactive Compounds from Acronychia Pedunculata as a Potential Inhibitor of HER2 in Colorectal Cancer

Abstract

ABSTRACT Colorectal cancer (CRC) is a pervasive malignancy that stands as a prominent contributor to global cancer-related mortality. Among the numerous causative factors, the overexpression of human epidermal growth factor receptor 2 (HER2) is notably linked to CRC progression. Acronychia (A.) pedunculata has a longstanding history in folk medicine due to its multifaceted medicinal attributes. This study aimed to assess the potential of specific bioactive compounds derived from A. pedunculata for their inhibition of HER2 in CRC, utilizing in silico analysis. The compounds were systematically evaluated through a series of computational analyses. Drug-likeness assessment, pharmacokinetic evaluation, and toxicity analysis were conducted. Molecular docking studies were performed to investigate binding affinities with the HER2 target. Additionally, bioavailability radar analysis was employed to predict oral bioavailability, while molecular target prediction provided insights into potential protein interactions. All 12 compounds demonstrated favorable drug-likeness properties and adherence to Lipinski’s rule of five, indicative of the potential for good oral bioavailability. Four compounds were found to have no toxicological endpoints. Molecular docking revealed two compounds, namely caryophylla-4 (14), 8 (15)-dien-5alpha-ol and (-)-globulol, which showed promising binding affinities between several compounds and HER2. From this study, two leads were identified from A. pedunculata. Further experimental studies are required to validate the action of leads.