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.

Forensic Imaging for Causal Investigation of Death

A 63-year-old man was found in the street after overrun by a car. Postmortem CT revealed multiple bone fractures, but surprisingly all without any relevant hemorrhage which would have been expected under such circumstances. A round radiopaque formation was found in the duodenum, which was reminiscent of ingested tablets. The toxicological analysis revealed high concentrations of zopiclone and alcohol. By combining radiologic and forensic results, zopiclone and alcohol intoxication were concluded as the cause of death, followed by a postmortem overrun accident.

The present study situation and application prospect of nail analysis for abused drugs / 法医学杂志

In forensic toxicology analysis, various types of biological samples have their own special characteristics and scope of applications. In this article, the physiological structure of nails, methods for collecting and pre-processing samples, and for analyzing some poisons and drugs in the nails are reviewed with details. This paper introduces the influence factors of drug abuse of the nails. The prospects of its further applications are concluded based on the research results. Nails, as an unconventional bio-sample without general application, show great potential and advantages in forensic toxicology.

effect of ciprofloxacin and clarithromycin on sildenafil oral bioavailability in human volunteers

Sildenafil is the first oral therapeutic agent for the management of male erectile dysfunction. Its oral bioavailability is only 40% due to extensive presystemic elimination, mainly by CYP3A4. This study examined the effect of coadministration of ciprofloxacin or clarithromycin which inhibit CYP3A4 on the bioavailability and pharmacokinetics of sildenafil. Twelve healthy male volunteers received sildenafil alone or after pretreatment with the inhibitors in a balanced three-way crossover design. The pharmacokinetic analysis showed that ciprofloxacin coadministration with sildenafil significantly increased the AUC from 1336 +/- 407 to 2751 +/- 968 micro g hr/L and the C max from 236 +/- 71 to 478 +/- 210 micro g/L. The CL tot/F was decreased from 40.1 +/- 9.9 to 20.9 +/- 8.6 L/hr and the Vd/F from 134.9 +/- 9.9 to 89.1 +/- 31.8 L, without affecting sildenafil elimination and absorption rate constants. Similarly, clarithromycin coadministration increased sildenafil AUC from 1336 +/- 407 to 2920 +/- 666 microg hr/L and C max from 236 +/- 71 to 520 +/- 176 microg/L. The CL tot/F significantly decreased from 40.1 +/- 9.9 to 18.1 +/- 5.0 L/hr and the Vd/F from 134.9 +/- 9.9 to 71.6 +/- 27.4 L, without affecting sildenafil elimination and absorption rate constants. These results indicate that coadministration of ciprofloxacin and clarithromycin significantly increased sildenafil bioavailability which can be inhibitory effect of ciprofloxacin and clarithromycin on CYP3A4. Dose adjustment of sidenafil is thus necessary when administered with such drugs

Colorimetric determination of piperazine.

A sensitive method for the quantitative determination of piperazine is described. The method is precise and responds linearly from 25 g to 500 mug and above of the material. The procedure is based on the formation of a complex of piperazine with reineckate in neutral or acid medium. The complex can be separated by centrifugation. It is then dissolved in acetone and estimated at 530 nm in a colorimeter. Piperazine present in trichloroacetic acid extractrs of biological samples can also be estimated by this method.