Rational design and antibacterial assessment of novel pyranopyrazole derivatives: a combined experimental and in silico study
Abstract
Pyranopyrazole derivatives were synthesized via multicomponent reactions and characterized using spectroscopic techniques including IR, 1H-NMR, 13C-NMR, and mass spectrometry. In vitro antibacterial evaluation revealed that compounds 2b, 3a, 5b, and 7b exhibited significant activity against Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis), while compounds 4b, 4d, 6b, and 8b demonstrated potent activity against Gram-negative bacteria (Pseudomonas aeruginosa and Escherichia coli). Quantum chemical calculations at the DFT/B3LYP/6-31G(d,p) level revealed HOMO–LUMO energy gaps ranging from 4.50 to 5.38 eV, with lower energy gaps correlating with enhanced antibacterial activity. Molecular electrostatic potential (MEP) analysis identified key electron-rich and electron-deficient regions responsible for target recognition. In silico molecular docking studies against tyrosyl-tRNA synthetase, an essential bacterial enzyme, demonstrated strong binding affinities with binding energies ranging from −7.84 to −11.30 kcal/mol and calculated inhibition constants (Ki) of 5.23 to 1790 nM. Key interactions involved hydrogen bonding and π-π stacking with active site residues Tyr34, His48, Asp177, and Gln196. ADME property predictions indicated favorable drug-like characteristics with compliance to Lipinski’s Rule of Five and high gastrointestinal absorption. These outstanding results could be due to the presence of aromatic moiety, halogen atom and cyano-group which enhance…
How strong is the evidence?
Evidence Hub reads this as a experimental / empirical study, done in 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
- Chaos and quantum thermalization
- The Dalton quantum chemistry program system
- Cord Blood Leptin and Adiponectin as Predictors of Adiposity in Children at 3 Years of Age: A Prospective Cohort Study
- Quantitative metabolomics by H-NMR and LC-MS/MS confirms altered metabolic pathways in diabetes
- Stable adiabatic quantum batteries
- A novel self-lipid antigen targets human T cells against CD1c(+) leukemias
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.