Design, synthesis, and antibacterial evaluation of new Schiff’s base derivatives bearing nitroimidazole and pyrazole nuclei as potent E. coli FabH inhibitors

Abstract

New Schiff's base derivatives 5a-j have been synthesized by reaction between 5-aryloxypyrazole-4-carbaldehydes 3a-j and 2-(2-methyl-5-nitro-1H-imidazol-1-yl)acetohydrazide 4 in the presence of nickel (II) nitrate as a catalyst in ethanol at room temperature with good yield (75-88 %). All compounds were tested for antibacterial properties and inhibition of E. coli FabH. Of the compounds studied, the majority of the compounds showed effective antibacterial properties and inhibition of E. coli FabH activity. Compound 5i showed the most effective inhibition (IC 50 = 4.6 ± 0.2 lM) by binding into the active site of the E. coli FabH receptor with minimum binding energy (DG b = -54.2961 kcal/mol). The binding was stabilized by two hydrogen bonds, two p-p, and three p-cation interactions.

Novel Pyrazole-Hydrazone Derivatives Containing an Isoxazole Moiety: Design, Synthesis, and Antiviral Activity

“…In recent years, literature revealed that pyrazole derivatives had a wide range of biological activities, such as antibacterial [ 5 , 6 , 7 ], fungicidal [ 8 , 9 , 10 ], insecticidal [ 10 , 11 , 12 , 13 ], antiviral [ 14 , 15 ], and herbicidal [ 16 , 17 ] activities. In our previous work, we reported a series of pyrazole derivatives which had better insecticidal activity against Plutella xylostella [ 18 ].…”

An Updated Review on the Synthesis and Antibacterial Activity of Molecular Hybrids and Conjugates Bearing Imidazole Moiety

“…In 2015, Sangani, Zhu, and coworkers [56] synthesised Schiff's base derivatives 87a-j bearing 5-nitroimidazole and pyrazole moieties by Ni(NO 3 ) 2 •6H 2 O-catalysed reaction of 5-aryloxypyrazole-4-carbaldehydes 88a-j [57] with 2-(2-methyl-5-nitro-1H-imidazol-1-yl) acetohydrazide (67) [58] in EtOH at room temperature. As shown in Scheme 16, this reaction provided hybrids 87a-j in 75-88% yield.…”

Researches and applications of nitroimidazole heterocycles in medicinal chemistry

“…含有脂肪胺乙基结构的卟啉衍生物43 用途广泛的合成药物中受欢迎且可靠的官能团之 一 [102,103] . 在脂肪胺乙基上引入羰基形成的酰胺类衍生 物44和45 (图5)对大肠杆菌的抑制浓度分别为MIC= 3.13 µg/mL, IC 50 =4.60 µM, 二者的抗菌活性均与广谱 抗生素卡那霉素(Kanamycin)相当, 其中酰胺键通过与 大肠杆菌的氨基酸残基进行氢键结合, 阻碍其生物合 成, 具有潜在的蛋白合成酶抑制活性 [104,105] .…”