RESUMEN
Aim: This study was designed to synthesize a novel series of terpyridines with potential antibacterial properties, targeting multidrug resistance. Materials & methods: Terpyridines (4a-h and 6a-c) were synthesized via a one-pot multicomponent reaction using 2,6-diacetylpyridines, benzaldehyde derivatives and malononitrile or ethyl 2-cyanoacetate. The reactions, conducted under grinding conditions with glacial acetic acid, produced high-yield compounds, confirmed by spectroscopic data. Results: The synthesized terpyridines exhibited potent antibacterial activity. Notably, compounds 4d and 4h demonstrated significant inhibition zones against Staphylococcus aureus and Bacillus subtilis, outperforming ciprofloxacin. Conclusion: Molecular docking studies highlighted compounds 4d, 4h and 6c as having strong binding affinity to DNA gyrase B, correlating with their robust antibacterial activity, suggesting their potential as effective agents against multidrug-resistant bacterial strains.
Asunto(s)
Antibacterianos , Staphylococcus aureus , Simulación del Acoplamiento Molecular , Antibacterianos/farmacología , Antibacterianos/química , Girasa de ADN/metabolismo , Pruebas de Sensibilidad Microbiana , Inhibidores de Topoisomerasa II/farmacología , Inhibidores de Topoisomerasa II/química , Relación Estructura-Actividad , Estructura MolecularRESUMEN
Mannich bases consisting of 1,3,4-oxadiazole-2-thione (3 a-3 l) bearing various substituents were synthesized and found potent jack bean urease inhibitors. The prepared compounds showed significantly good inhibitory activities with IC50 values from 9.45±0.05 to 267.42±0.23â µM. The compound 3 k containing 4-chlorophenyl (-R) and 4-hydroxyphenyl (-R') was most active with IC50 9.45±0.05â µM followed by 3 e (IC50 22.52±0.15â µM) in which -R was phenyl and -R' was isopropyl group. However, when both -R and -R' were either 4-chlorophenyl groups (3 l) or only -R' was 4-nitrophenyl (3 i), both compounds were found inactive. The detailed binding affinities of the produced compounds with protein were explored through molecular docking and data-supported in-vitro enzyme inhibition profiles. Drug likeness was confirmed by in silico ADME investigations and molecular orbital analysis (HOMO-LUMO) and electrostatic potential maps were got from DFT calculations. ESP maps exposed that there are two potential binding sites with the most positive and most negative parts.