Synthesis and in silico study of 2-furyl(4-{4-[(substituted)sulfonyl]benzyl}-1-piperazinyl)methanone derivatives as suitable therapeutic agents

Abstract In the study presented here, a new series of 2-furyl(4-{4-[(substituted)sulfonyl]benzyl}-1-piperazinyl)methanone derivatives was targeted. The synthesis was initiated by the treatment of different secondary amines (1a-h) with 4-bromomethylbenzenesulfonyl chloride (2) to obtain various 1-{[4-(bromomethyl)phenyl]sulfonyl}amines (3a-h). 2-Furyl(1-piperazinyl)methanone (2-furoyl-1-piperazine; 4) was then dissolved in acetonitrile, with the addition of K2CO3, and the mixture was refluxed for activation. This activated molecule was further treated with equi-molar amounts of 3a-h to form targeted 2-furyl(4-{4-[(substituted)sulfonyl]benzyl}-1-piperazinyl)methanone derivatives (5a-h) in the same reaction set up. The structure confirmation of all the synthesized compounds was carried out by EI-MS, IR and 1H-NMR spectral analysis. The compounds showed good enzyme inhibitory activity. Compound 5h showed excellent inhibitory effect against acetyl- and butyrylcholinesterase with respective IC50 values of 2.91±0.001 and 4.35±0.004 µM, compared to eserine, a reference standard with IC50 values of 0.04±0.0001 and 0.85±0.001 µM, respectively, against these enzymes. All synthesized molecules were active against almost all Gram-positive and Gram-negative bacterial strains tested. The cytotoxicity of the molecules was also checked to determine their utility as possible therapeutic agents.

Recovery of plasmatic cholinesterase activity in a neotropical fish Prochilodus lineatus (Pisces, Curimatidae) exposed to organophosphorous pesticides.

The objective was to determine the plasmatic enzyme cholinesterase recovery, after being inhibited by an organophosphorous in juveniles of Prochilodus lineatus. Fish were exposed 12 h to a sublethal concentration of 1 mg/l of monocrotophos, and immediately placing in clean water during 12, 24, 48 and 96 h to detoxification. After this period, blood was extracted and plasma were used for the quantification of cholinesterase. The results showed a enzymatic inhibition of 91.9%, 55.1%, 50.4% and 33.4% with 12, 24, 48 and 96 h of recovery, respectively. The enzymatic activity spreads to be normalized with the course of hours and the degree of inhibition obtained initially was very high and sustained in the first 48 h.