Assessment and Density Functional Theory of Bioactive Compounds of Curcuma longa L. Root Responsible for Its...

Background/Objectives: Cardiovascular diseases (CVDs) and cancer remain major global health challenges and are among the leading causes of mortality worldwide, including in Kuwait. Medicinal plants are important sources of bioactive compounds with therapeutic potential. This study aimed to identify the phytochemical constituents of Curcuma longa L. root extract and evaluate their potential cardioprotective and anticancer activities using integrated computational approaches. Methods: Phytochemical profiling of Curcuma longa root extract was performed using gas chromatography-mass spectrometry (GC-MS). The identified compounds were evaluated through molecular docking against selected cardiovascular- and cancer-related targets, including HMG-CoA reductase, phosphoinositide 3-kinase (PI3K), cyclin-dependent kinase 6 (CDK6), and HER2 kinase receptors. Protein-ligand interactions were analyzed to determine binding stability. Biological activity prediction and pharmacokinetic properties were assessed using PASS prediction and SwissADME tools, while density functional theory (DFT) calculations were conducted to investigate electronic and quantum chemical characteristics associated with ligand reactivity. Results: GC-MS analysis identified seventeen phytochemical constituents with retention times ranging from 7.57 to 32.70 min. The major compounds detected were 2-oxo-cyclooctaneacetic acid (30.88%), curlone (20.99%), and tumerone (13.85%). Molecular docking revealed favorable binding affinities for α-curcumene, caryophyllene, bergamotene, cyclohexene derivatives, tumerone, curlone, and (6R,7R)-bisabolone against the selected targets, with interaction profiles comparable to reference drugs. PASS and SwissADME analyses indicated promising biological activities, acceptable drug-likeness, and favorable pharmacokinetic properties. DFT analysis demonstrated that curlone and tumerone possessed stable electronic configurations and favorable reactivity profiles. Conclusions: The findings suggest that bioactive compounds from Curcuma longa may serve as promising lead candidates for the development of cardioprotective and anticancer agents. However, further experimental validation through in vitro and in vivo studies is required to confirm these computational predictions.