Discovery of Bioactive compounds from Syzygium cumini L. Targeting PI3Kɑ for Breast Cancer Therapy: An Integrated Computational Approach

Introduction: Breast cancer is the most prevalent malignancy and the common type of cancer in women globally, accounting for more than 10% of newly diagnosed cancer cases annually. In the present research, we evaluated the potential anticancer effects of phytochemicals from Syzygium cumini L. against breast cancer acting via inhibition of PI3Kɑ through ADMET and molecular docking approach.

Methods: The phytochemicals from Syzygium cumini were screened for their toxicity and drug-likeness through ADMET analysis using SwissADME (https://www.swissadme.ch/) followed by molecular docking of the most accepted compound using maestro 13.7.125 (Schrodinger Ltd. USA) software. The protein binding receptors (PDB ID: 4L2Y) were obtained from protein data bank (https://www.rcsb.org/).

Results: This study investigated the molecular mechanism underlying the anticancer activity of selected phytochemicals against breast cancer. A total 12 compounds were initially screened for drug likeness and its pharmacokinetics properties through ADMET profiling, from which four compounds, including standard drug paclitaxel satisfied the pre-defined drug-likeness and pharmacokinetics criteria. Subsequently, docking was performed to evaluate their binding interactions against PI3Kɑ. Among the evaluated compounds, Gallic acid exhibited the strongest binding interactions with a docking score of -5.49 Kcal/mol.

Conclusion: The integration of computational approaches enables the systematic identification of bioactive phytochemicals for anticancer potential, prediction of molecular targets and signalling pathways and comprehensive evaluation of their pharmacokinetics, toxicological properties and drug-likeness properties, thereby accelerating the discovery and optimization of novel therapeutic candidates.