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Oxidation of o-nitroaniline with sodium hypochlorite afforded benzofurazan oxide in 96 % yield, and treatment of benzofurazan oxide with acetylacetone in the presence of triethylamine gave 2-acetyl-3-methyl-quinoxaline- -1,4-dioxide in 94 % yield. Finally, condensation of 2-acetyl-3-methyl-quinoxaline- 1,4-dioxide with benzaldehyde using 4-(dimethylamino)pyridinium acetate as a catalyst led to quinocetone in 95 % yield. Subsequently, reduction of the synthesized quinocetone with sodium dithionite resulted in two deoxy derivatives, 1-(3-methyl-4-oxido-2-quinoxalinyl)-3-phenyl-2-propen-1-one and 1-(3-methyl-2-quinoxalinyl)-3-phenyl-2-propen-1-one in 88.5 and 92 % yield, respectively. Furthermore, the synthesized quinocetone, and its deoxy derivatives were characterized by 1H-NMR, 13C-NMR and elemental analysis.

Carbapenem-resistant Escherichia coli ( E. coli ) strains are widely distributed and spreading rapidly, creating significant challenges for clinical therapeutics. NDM-5, a novel mutant of New Delhi Metallo-β-Lactamase-1 (NDM-1), exhibits high hydrolase activity toward carbapenems. Since the genetic backgrounds of clinically isolated carbapenem-resistant E. coli are heterogeneous, it is difficult to accurately evaluate the impact of bla NDM-5 on antibiotic resistance. Herein, E. coli BL21 was transformed with a plasmid harboring bla NDM-5 , and the resultant strain was named BL21 (pET-28a- bla NDM-5 ). Consistent with the findings of previous studies, the introduction of exogenous bla NDM-5 resulted in markedly greater resistance of E. coli to multiple β-lactam antibiotics. Compared with BL21 (pET-28a), BL21 (pET-28a- bla NDM-5 ) exhibited reduced motility but a significant increase in biofilm formation capacity. Furthermore, transcriptome sequencing was conducted to compare the transcriptional differences between BL21 (pET-28a) and BL21 (pET-28a- bla NDM-5 ). A total of 461 differentially expressed genes were identified, including those related to antibiotic resistance, such as genes associated with the active efflux system ( yddA , mcbR and emrY ), pili ( csgC , csgF and fimD ), biofilm formation ( csgD , csgB and ecpR ) and antioxidant processes ( nuoG ). Finally, the pGS21a plasmid harboring bla NDM-5 was transformed into E. coli Rosetta2, after which the expression of the NDM-5 protein was induced using isopropyl-β-D-thiogalactoside (IPTG). Using glutathione-S-transferase (GST) pull-down assays, total proteins from E. coli were scanned to screen out 82 proteins that potentially interacted with NDM-5. Our findings provide new insight into the identified proteins to identify potential antibiotic targets and design novel inhibitors of carbapenem-resistant bacteria., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Gao, Wang, Lu, Ji, Zhang, Yang, Cheng, Sun and Qu.)

The objective of this study was to prepare a new compound fenbendazole tablet containing 29.7 % fenbendazole, 1.50 % praziquantel and 0.059 % ivermectin for oral administration. The tablets were successfully prepared using mannitol as filler agent, polyvinyl polypyrrolidone as disintegrant, 5 % povidone (PVAK30) as a binder agent and magnesium stearate as lubricant. The appearance, hardness, fragility, time limit of disintegration and fenbendazole dissolution at 45 min all met the technical standards of the Ministry of Agriculture for the People's Republic of China. We used high performance liquid chromatography and electrospray-mass spectrometry for drug detection. Oral administration of 100 mg/kg fenbendazole, 5 mg/kg praziquantel and 0.2 mg/kg ivermectin using a non-compartmental model defined peak plasma concentrations (Cmax) of 495, 826, 73 ng/mL, and 218 ng/mL for the metabolite oxfendazole, respectively. The area under the curve (AUClast) values for these drugs were 4653, 1045, 1971 and 5525 h×ng/mL, respectively. This study enriches the pharmacokinetic data of compound fenbendazole tablets using dogs as a model system. The new tablet formulation was assimilated quickly and systemically and this study will be beneficial for the clinical application of parasite treatments in dogs.