antimicrobial activities, molecular docking and density functional theory (DFT) evaluation of natural product-based vanillin derivatives featuring halogenated azo dyes.

Chemical modification of active scaffolds from natural products has gained interest in pharmaceutical industries. Nevertheless, the metabolites extraction is time-consuming while the lead is frequently mismatched with the receptor. Here, the diazo coupling approach was introduced to generate a series of vanillin derivatives featuring halogenated azo dyes (). The vanillin derivatives showed effective inhibition of (7-9 mm) and (7-8 mm) compared to the parent vanillin, while had the highest inhibition zone (9 mm) against comparable to the reference ampicillin. The presence of N = N, C = O, -OH, -OCH3 and halogens established strategic binding interactions with the receptor. The potential vanillin-azo as an antimicrobial drug was supported by docking with penicillin-binding proteins and DFT (using Gaussian 09) with binding affinity -7.5 kcal/mol and energy gap (Egap) 3.77 eV, respectively. This study represents a significant advancement in drug discovery for effective antibiotics with excellent properties.