4 research outputs found
LCâMSâMS Method for the Analysis of New Non-Imidazole Histamine H3 Receptor Antagonist 1-[3-(4-tert-Butylphenoxy)propyl]piperidine in Rat SerumâApplication to Pharmacokinetic Studies
A sensitive and specific liquid chromatography electrospray ionisationâtandem mass spectrometry method for determination of new non-imidazole histamine H3 receptor antagonist 1-[3-(4-tert-butylphenoxy)propyl]piperidine (DL76) in rat serum has been developed and validated. Chromatography was performed on a XBridgeâą C18 analytical column (2.1 Ă 30 mm, 3.5 ”m, Waters, Ireland) with gradient elution using a mobile phase containing acetonitrile and water with an addition of 0.1% of formic acid. Detection was achieved by an Applied Biosystems MDS Sciex (Concord, Ontario, Canada) API 2000 triple quadrupole mass spectrometer. Electrospray ionization (ESI) was used for ion production. The limit of detection in the SRM mode was found to be 0.5 ng mLâ1. The limit of quantification was 1 ng mLâ1. The precision and accuracy for both intra- and inter-day determination of DL76 ranged from 1.65 to 15.09% and from 88.74 to 113.43%. The results of this analytical method validation allow to carry out pharmacokinetic studies in rats. The method was used for the pilot study of the pharmacokinetic behavior of DL76 in rats after intravenous administration
Selenocompounds as Novel Antibacterial Agents and Bacterial Efflux Pump Inhibitors
Bacterial multidrug resistance is becoming a growing problem for public health, due to
the development and spreading of bacterial strains resistant to antimicrobials. In this study, the
antibacterial and multidrug resistance reversing activity of a series of seleno-carbonyl compounds
has been evaluated. The effects of eleven selenocompounds on bacterial growth were evaluated in
Staphylococcus aureus, methicillin resistant S. aureus (MRSA), Enterococcus faecalis, Escherichia coli, and
Chlamydia trachomatis D. The combination effect of compounds with antibiotics was examined by the
minimum inhibitory concentration reduction assay. Their efflux pump (EP) inhibitory properties
were assessed using real-time fluorimetry. Relative expressions of EP and quorum-sensing genes
were studied by quantitative PCR. Results showed that a methylketone selenoester had remarkable
antibacterial activity against Gram-positive bacteria and potentiated the activity of oxacillin in MRSA.
Most of the selenocompounds showed significant anti-chlamydial effects. The selenoanhydride
and the diselenodiester were active inhibitors of the AcrAB-TolC system. Based on these results
it can be concluded that this group of selenocompounds can be attractive potential antibacterials
and EP inhibitors. The discovery of new derivatives with a significant antibacterial activity as novel
selenocompounds, is of high impact in the fight against resistant pathogen
Selenocompounds as Novel Antibacterial Agents and Bacterial Efflux Pump Inhibitors
Bacterial multidrug resistance is becoming a growing problem for public health, due to
the development and spreading of bacterial strains resistant to antimicrobials. In this study, the
antibacterial and multidrug resistance reversing activity of a series of seleno-carbonyl compounds
has been evaluated. The effects of eleven selenocompounds on bacterial growth were evaluated in
Staphylococcus aureus, methicillin resistant S. aureus (MRSA), Enterococcus faecalis, Escherichia coli, and
Chlamydia trachomatis D. The combination effect of compounds with antibiotics was examined by the
minimum inhibitory concentration reduction assay. Their efflux pump (EP) inhibitory properties
were assessed using real-time fluorimetry. Relative expressions of EP and quorum-sensing genes
were studied by quantitative PCR. Results showed that a methylketone selenoester had remarkable
antibacterial activity against Gram-positive bacteria and potentiated the activity of oxacillin in MRSA.
Most of the selenocompounds showed significant anti-chlamydial effects. The selenoanhydride
and the diselenodiester were active inhibitors of the AcrAB-TolC system. Based on these results
it can be concluded that this group of selenocompounds can be attractive potential antibacterials
and EP inhibitors. The discovery of new derivatives with a significant antibacterial activity as novel
selenocompounds, is of high impact in the fight against resistant pathogen