Design, synthesis, characterization, pharmacological evaluation and in silico ADMET and molecular docking and dynamics simulations of a novel series of N-substituted pyrazole from chalcone derivatives

Abstract

Abstract A novel series of N -pyrazolyl-thienopyrimidine and pyridopyrimidine hybrids was synthesized and characterized using spectroscopic methods. Compounds 4c , 5c , and 12 exhibited superior antibacterial potency compared to Levofloxacin, with molecular docking revealing strong binding to key bacterial targets (e.g., DNA gyrase, Neuraminidase). In-silico ADMET analysis confirmed favorable drug-like properties and low toxicity for 4c , supported by stable molecular dynamics interactions. Additionally, 5c and 12 demonstrated potent anti-inflammatory activity surpassing Celecoxib, with reduced ulcerogenicity. These findings introduce a promising new class of dual-action agents for antibacterial and anti-inflammatory drug development.