Synthesis, molecular docking, ADMET studies and biological evaluation of fused pyrazolopyridopyrimidine derivatives as antioxidant and antimicrobial agents

Abstract

Abstract This study describes the design, synthesis, and biological evaluation of fused pyrazolopyridopyrimidine analogues as potential antimicrobial and antioxidant agents. The chemical structures of the newly synthesized compounds were confirmed by elemental analyses and spectroscopic methods. The compounds were screened for antimicrobial activity against Escherichia coli ATCC 25,915, Staphylococcus aureus ATCC 25,923, Enterococcus faecalis ATCC 29,212, Pseudomonas aeruginosa ATCC 10,145, and Streptococcus mutans ATCC 25,175. Compound 7 exhibited pronounced inhibitory effects. Evaluation of antioxidant potential using the DPPH radical scavenging assay revealed that compound 15 displayed superior activity, with inhibition values of 44.44 ± 0.80%, 16.50 ± 0.90%, and 0.0% at concentrations of 2.0, 1.0, and 0.5 mg/mL, respectively. To elucidate the molecular basis of these activities, docking studies were performed, which demonstrated favorable binding interactions with key microbial and antioxidant-related targets. Furthermore, ADMET profiling and drug-likeness assessments confirmed that compounds 7, 9, 11, and 15 adhere to Lipinski’s Rule of Five, suggesting favorable oral bioavailability and promising pharmacokinetic properties. Taken together, these findings highlight fused pyrazolopyridopyrimidines as structurally promising scaffolds for the development of novel antimicrobial and antioxidant therapeutics, warranting further structural optimization and preclinical investigation.