Experimental and theoretical investigation into the structural and anticancer properties of sulfadiazine-derived azo dyes: A DFT and molecular docking approach.

Four sulfadiazine-based azo dyes (P1-P4) were synthesized via electrophilic coupling with barbituric acid derivatives and 4-hydroxycoumarin. Cytotoxicity screening against MDA-MB-231 human breast cancer cells revealed IC₅₀ values of 36.34 μg/mL (P1), 47.32 μg/mL (P2), 21.50 μg/mL (P3), and 23.64 μg/mL (P4). Molecular docking against human aromatase (PDB: 4GL7) gave binding energies from -6.51 to -7.34 kcal mol-1, with P4 showing the strongest affinity (-7.34 kcal mol-1) through hydrogen bonds (Gly156, Val158, Glu281) and π-interactions (Arg159, Met276). DFT (B3LYP/6-31G(d,p)) and TD-DFT calculations showed that experimental UV-Vis λₘₐₓ (386-412 nm) are red shifted relative to theoretical values (313-379 nm) due to solvent effects. NBO analysis identified π → π* delocalization as the main stabilizing interaction. The first hyperpolarizability (βₜₒₜₐₗ) of P4 is 8.35 × 10-30 e.s.u., ∼22-fold higher than that of urea, indicating strong nonlinear optical potential. Mulliken charges identified the most reactive sites for electrophilic/nucleophilic attacks. The combined experimental and computational data support P3 and P4 as promising anti-breast cancer leads and NLO materials.