Pyrazolopyrimidine and 4-pyrimidylpyrazolone analogues as promising novel sulfa drugs: Design, synthesis, antibacterial, antibiofilm, antiquorum agents, computational details and molecular docking studies

In the current study, we aimed at creating novel molecules with a sulfonamide group that can be produced in simple ways. A series of novel N-arylsulfonamide pyrazolopyrimidine 3a,b and 4-pyrimidylpyrazolone 7a-h derivatives were synthesized by simple and efficient methods. Several spectroscopic techniques were used to characterize the structures of the synthesized compounds and confirmed by ab-initio density functional theory calculations in water solvent. The same calculation method was also used to shed light on the reaction mechanisms in terms of thermodynamic concepts. In vitro, all synthetic target compounds were examined using the agar well diffusion method for antibacterial activity. Compounds 7a and 7b exhibited the most potent antibacterial activity against 23 Pseudomonas aeruginosa clinical isolates with minimum inhibitory concentrations ranged from 32 to 256 mu g/mL and 16-256 mu g/mL, respectively. Both compounds displayed a significant reduction in exopolysaccharide quantity, cell surface hydrophobicity, biofilm formation, and quorum sensing by the tested P. aeruginosa isolates with different percentages. The synthesized compounds were further studied employing molecular docking techniques to predict their binding modes into active site of the target protein. The results show that the investigated compounds exhibit high binding affinities (ca. 10 kcal/mol) toward Pseudomonas aeruginosa PBP3 protein confirming their ability in the treatments of the infections caused by P. aeruginosa bacteria. More future studies are recommended to investigate the activities of these compounds in vivo and in clinical studies.