One-Pot Synthesis of Pyrimido[4,5-d]pyrimidine Derivatives and Investigation of Their Antibacterial, Antioxidant, DNA-Binding and Voltammetric Characteristics

Dihydropyrimidinones (DHPMs), 4 a-f and 6 a-f is reported and were characterized by ¹H-NMR, ¹³C-NMR, FT-IR and LC–MS. The synthesized compounds were evaluated for their antibacterial activity against Staphylococcus aureus (S.aureus), Bacillus subtilis (B. subtilis), Salmonella typhi (S. typhi) and Pseudomonas aeruginosa (P. aeruginosa). Among the test samples compounds, 5-(4-hydroxy-3-methoxyphenyl)-7-imino-1,3,5,6,8-pentahydropyrimido[4,5-d]pyrimidine-2,4-dione (6 c) and 5-(4-hydroxy-3,5-dimethoxyphenyl)-1,3-N,N-dimethyl-7-thioxo-5,6,8-trihydropyrimido[4,5-d]pyrimidine-2,4-dione (4 d) were more potent against S. aureus and B. subtilis. Whereas 5-(4-hydroxy-3-methoxyphenyl)-1,3-N,N-dimethyl-5,6,8-trihydropyrimido[4,5-d]pyrimidine-2,4,7-trione (6 e) and 5-(4-hydroxy-3,5-dimethoxyphenyl)-1,3-N,N-dimethyl-5,6,8-trihydropyrimido[4,5-d]pyrimidine-2,4,7-trione (4 e) showed good inhibition against S. typhi and P. aeruginosa which were well supported by computational interaction and DNA binding studies. Compound 5-(4-hydroxy-3,5-dimethoxyphenyl)-7-imino-1,3,5,6,8-pentahydropyrimido[4,5-d]pyrimidine-2,4,7-trione (4 c) exhibited potent scavenging activity with IC₅₀ of 8.30 mg/ml. Furthermore, Cyclic Voltammetric analysis disclosed that 5-(4-hydroxy-3,5-dimethoxyphenyl)-7-thioxo-1,3,5,6,8-pentahydropyrimido[4,5-d]pyrimidine-2,4-dione (4 a), 5-(4-hydroxy-3,5-dimethoxyphenyl)-1,3,5,6,8-pentahydropyrimido[4,5-d]pyrimidine-2,4,7-trione (4 b), 4 c, 6 d, 6 e, and 6 f showed redox behavior.