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 (1a-h). The vanillin derivatives showed effective inhibition of S. aureus (7-9 mm) and E. coli (7-8 mm) compared to the parent vanillin, while 1b had the highest inhibition zone (9 mm) against S. aureus 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 in silico 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.
In searching for drugs from natural product scaffolds has gained interest among researchers. In this study, a series of twelve halogenated thiourea (ATX 1-12)via chemical modification of aspirin (a natural product derivative) and evaluated for cytotoxic activity against nasopharyngeal carcinoma (NPC) cell lines, HK-1 via MTS-based colorimetric assay. The cytotoxicity studies demonstrated that halogens at meta position of ATX showed promising activity against HK-1 cells (IC50 value ≤15 µM) in comparison to cisplatin, a positive cytotoxic drug (IC50 value =8.9 ± 1.9 µM). ATX 11, bearing iodine at meta position, showed robust cytotoxicity against HK-1 cells with an IC50 value of 4.7 ± 0.7 µM. Molecular docking interactions between ATX 11 and cyclooxygenase-2 demonstrated a robust binding affinity value of -8.1 kcal/mol as compared to aspirin's binding affinity value of -6.4 kcal/mol. The findings represent a promising lead molecule from natural product with excellent cytotoxic activity against NPC cell lines.