Design of a Steroid-Flavonoid Hybrid for Multi-Target Modulation of Human Interleukins: Computational Evaluation

Chronic inflammation is mediated by interleukins (ILs), which are key in autoimmune, cardiovascular, and metabolic diseases. We report a novel hybrid molecule designed by combining pharmacophoric features of amentoflavone and vitamin D3. Molecular docking against IL-1β, IL-2, IL-4, IL-6, IL-8, IL-11, IL-12, and IL-17A demonstrated that the hybrid binds strongly across all IL targets, with affinities intermediate between amentoflavone (high potency, poor pharmacokinetics) and vitamin D3 (lower potency, favorable safety). ADMET prediction indicated improved drug-likeness, bioavailability, and reduced toxicity relative to amentoflavone. The hybrid scaffold integrates the hydrophobicity and rigidity of the steroid core with the polar, hydrogen-bonding capacity of the flavonoid moiety, representing a promising natural product-inspired NCE. These findings suggest potential for multi-target modulation of pro-inflammatory cytokines and support further experimental evaluation.