Design, Synthesis, and Antibacterial Evaluation of Pyrazole Pyrimidine Hybrids: Integrative In Vitro and In Silico Studies
Abstract
Abstract Several novel pyrimidine–pyrazole hybrids were synthesized and evaluated for their antimicrobial potential against diverse bacterial pathogens, focusing on targeting penicillin‐binding protein 3 (PBP3), a key enzyme in bacterial cell wall synthesis. Among the tested derivatives, seven derivatives exhibited significant antibacterial activity against E. faecium at 50–200 µg/mL with the cyclopentane‐substituted compound ( 6d ) showing the highest activity (50 µg/mL). Notably, the 3‐fluoro,5‐trifluoromethyl compound ( 6a ) demonstrated broad‐spectrum activity (200 µg/mL) against S. aureus , E. faecium, A. baumannii , and K. pneumoniae . Docking studies revealed strong binding affinity with HMG‐CoA synthase, an essential enzyme in bacterial metabolism. In silico pharmacokinetic predictions indicated favourable safety profiles and drug‐likeness. These results suggest pyrimidine–pyrazole hybrids as promising antibacterial agents targeting PBP3, warranting further investigation through enzymatic inhibition assays and in vivo studies.
How strong is the evidence?
Evidence Hub reads this as a simulation / modelling, done in cell cultures (in vitro) and computer models (in silico), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
Read the paper
Related studies
- Ferulic acid regulates the AKT/GSK-3β/CRMP-2 signaling pathway in a middle cerebral artery occlusion animal model
- Novel Pharmacokinetic/Pharmacodynamic Parameters Quantify the Exposure–Effect Relationship of Levofloxacin against Fluoroquinolone-Resistant Escherichia coli
- Photochemical behavior of levofloxacin
- Correlation Between Dissolution Profiles of Salt-Form Drugs in Biorelevant Bicarbonate Buffer and Oral Drug Absorption: Importance of Dose/ Fluid Volume Ratio
- Evaluation of the synergistic potential and mechanisms of action for de novo designed cationic antimicrobial peptides
- Synthesis of [11C]levofloxacin
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.