Synthesis of 4,4′-(4-Formyl-1H-pyrazole-1,3-diyl)dibenzoic Acid Derivatives as Narrow Spectrum Antibiotics for the Potential Treatment of Acinetobacter Baumannii Infections

Abstract

Acinetobacter baumannii has emerged as one of the most lethal drug-resistant bacteria in recent years. We report the synthesis and antimicrobial studies of 25 new pyrazole-derived hydrazones. Some of these molecules are potent and specific inhibitors of A. baumannii strains with a minimum inhibitory concentration (MIC) value as low as 0.78 µg/mL. These compounds are non-toxic to mammalian cell lines in in vitro studies. Furthermore, one of the potent molecules has been studied for possible in vivo toxicity in the mouse model and found to be non-toxic based on the effect on 14 physiological blood markers of organ injury.

Synthesis of 3,5-Bis(trifluoromethyl)phenyl-Substituted Pyrazole Derivatives as Potent Growth Inhibitors of Drug-Resistant Bacteria

“…Based on the activities, we found a good Structure Activity Relationship (SAR) of the product with respect to the substituents in the aniline moiety. The presence of a protic substituent, carboxylic acid, eliminated the activity of the compounds ( 12 and 13 ), which is in accordance with our previous findings [ 29 , 31 , 32 ]. The presence of lipophilic substituents (clog P = 7–8) on the phenyl ring of the aniline moiety increased the activity.…”

Unravelling the synthetic and therapeutic aspects of five, six and fused heterocycles using Vilsmeier–Haack reagent

“…In 2020, Delancey and group 42 produced 4,4-(4-formyl-1 H -pyrazole-1,3-diyl)dibenzoic acid from the reaction of hydrazones with V. H. reagent at 0 °C followed by stirring the reaction mixture at 70 °C for 5 hours, in excellent yield. Further novel 2-(1-benzyl-3-(4-fluorophenyl)-1 H -pyrazol-4-yl)-7-fluoro-4 H -chromen-4-ones were synthesized by utilizing this formyl pyrazole as substrate.…”

Development of 4-[4-(Anilinomethyl)-3-phenyl-pyrazol-1-yl] Benzoic Acid Derivatives as Potent Anti-Staphylococci and Anti-Enterococci Agents

“…Pyrazole nucleus has widely been found in approved drugs, such as apixaban (Eliquis @ ), celecoxib (Celecox @ ), and several others ( accessed on 8 July 2022). A myriad number of synthetic derivatives of this azole have been reported for their a nticancer [ 15 , 16 ], antibacterial [ 17 ], antiviral [ 18 ], and several other therapeutic properties [ 19 ]. In our research on azole derivatives as potent antibacterial [ 20 , 21 , 22 ] and antineoplastic agents [ 23 , 24 , 25 ], we found pyrazole-derived hydrazones are potent growth inhibitors of A. baumannii [ 21 , 26 ] and the aniline derivatives of pyrazoles are potent growth inhibitors of Gram-positive bacteria [ 22 , 27 ].…”