Scopoletin Derivatives for Cancer Therapy: Computational Design and VEGFR-2 Targeting Approach

Cancer will be the main cause for mortality by 2030, necessitating cost-effective and effective therapies. Numerous anticancer drugs exist, yet they frequently lead to significant side effects, positioning natural compounds as a viable alternative. Scopoletin, a coumarin derivative present in multiple plant species, exhibits a range of pharmacological effects, such as anti-inflammatory, antioxidant, and immunomodulatory activities. Recent investigation has identified scopoletin and its derivatives as having potential anticancer properties. The current research examines the design and assessment of scopoletin derivatives that went through chemical modifications to improve bioavailability, safety, and efficacy. Using in-silico methods, we evaluated scopoletin derivatives for drug-likeness, toxicity, and pharmacokinetics. VEGFR-2 overexpression is prevalent in various cancers, such as breast and cervical cancer. As a result, the VEGFR-2 kinase domain (PDB ID: 2XIR) was chosen as a target for molecular docking simulations. Ten scopoletin derivatives were evaluated for their activity against VEGFR-2, identifying potential inhibitors based on binding affinities ranging from -5 to -15 kcal/mol. The top-performing derivatives exhibited favorable interactions, needing further study for anticancer possibilities. This investigation establishes a basis for the development of scopoletin-derived anticancer agents highlighting improved structural and pharmacological properties.