Novel ionic liquids incorporated pyridazinone-vanillyl motifs: Synthesis, characterization, pharmacological survey and molecular docking

作者：Elshaarawy Reda F M^*; Soliman Mohamed H A; Zein Mohamed A E; Kheiralla Zeinab H; Abd El Bari Douaa A

来源：Journal of Molecular Liquids, 2018, 259: 144-153.

DOI：10.1016/j.molliq.2018.03.022

• Ionic liquids
• Pyridazinone-vanillyl
• Characterization
• Antimicrobial
• Docking study

Inspired by an urgent unmet medical need for development of potent and broad-spectrum antibiotics, we apply herein diverse strategies to obtain novel pyridazinone-vanillyl conjugates having a N(2)-arm of arylpropanamides (8a-c) or vanillyl ionic liquids (Val-ILs) (9a-d) motifs. These new pyridazinone-based antibiotic candidates display remarkable and broad-spectrum antimicrobial efficacy. Combined analysis of pharmacological results coupled with the in Silico derived parameters demonstrated the importance of the chemical nature of the arm in tuning the antimicrobial potency for the target compounds. For instance, 9b (with Val-IL arm) (MIC/MBC = 1.98/2.18 mu g/mL) is about 7-fold more potent than 8a (with neutral arm) (MIC/MBC = 13.50/14.12 mu g/ mL) as Anti-P. aeruginosa agent. The molecular docking study revealed that compound 8a was found to the most effective in binding to the active site of E. coli FabH (PDB code 1HNJ) with H-bonding, pi-stacking and hydrophobic groove interactions having minimum binding energy Delta G(b) = -14.00 kcal/mol.

• 出版日期2018-6-1