Facile synthesis, spectroscopic evaluation and antimicrobial screening of metal endowed triazole compounds.

The scientific interest in developing new complexes as inhibitors of bacterial biofilm related infections is constantly rising. The present work describes the chemical synthesis, structural and biological scrutiny of a triazole Schiff base ligand and its corresponding complexes. Triazole Schiff base, (2-methoxy-4-[(1H-1,2,4-triazol-3-ylimino)methyl]phenol) was synthesized from the condensation reaction of 3-amino-1,2,4-triazole and 4-hydroxy-3-methoxybenzaldehyde in an equimolar ratio. The triazole ligand (H2L) was characterized by physical (solubility, color, melting point), spectroscopic [UV-visible (UV-Vis), Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (1H-NMR) and mass spectra (MS)] and micro analysis to evaluate their elemental composition. The bidentate ligand was complexed with transition metal [VO(IV), Fe(II), Co(II), Ni(II), Cu(II) and Zn(II)] in 1:2 molar ratio. The complexes were characterized by physical (color, solubility, decomposition temperature, conductance and magnetic moment), FT-IR, UV-Vis and elemental analysis. Thermal stability and fluorescence properties of the compounds were also determined. Density functional theory based theoretical calculations were accomplished to gain more insight into spectroscopic properties. The frontier molecular orbital analysis revealed that the ligand was less reactive with reduced electron donating capability and more kinetic stability than complexes. The as-synthesized compounds were scrutinized for anti-bacterial and anti-fungal activity against selected strains. Cobalt complex exhibited highest antibacterial activity against Escherichia coli and nickel complex has shown highest antifungal activity against Aspergillus niger. All the compounds also showed good antioxidant activity. The theoretical results reflect consistency with the experimental findings signifying that such compounds could be the promising chemical scaffolds in the near future against microbial infectious.

Downregulation of the endogenous opioid peptides in the dorsal striatum of human alcoholics.

The endogenous opioid peptides dynorphins and enkephalins may be involved in brain-area specific synaptic adaptations relevant for different stages of an addiction cycle. We compared the levels of prodynorphin (PDYN) and proenkephalin (PENK) mRNAs (by qRT-PCR), and dynorphins and enkephalins (by radioimmunoassay) in the caudate nucleus and putamen between alcoholics and control subjects. We also evaluated whether PDYN promoter variant rs1997794 associated with alcoholism affects PDYN expression. Postmortem specimens obtained from 24 alcoholics and 26 controls were included in final statistical analysis. PDYN mRNA and Met-enkephalin-Arg-Phe, a marker of PENK were downregulated in the caudate of alcoholics, while PDYN mRNA and Leu-enkephalin-Arg, a marker of PDYN were decreased in the putamen of alcoholics carrying high risk rs1997794 C allele. Downregulation of opioid peptides in the dorsal striatum may contribute to development of alcoholism including changes in goal directed behavior and formation of a compulsive habit in alcoholics.

Asymmetry of the endogenous opioid system in the human anterior cingulate: a putative molecular basis for lateralization of emotions and pain.

Lateralization of the processing of positive and negative emotions and pain suggests an asymmetric distribution of the neurotransmitter systems regulating these functions between the left and right brain hemispheres. By virtue of their ability to selectively mediate euphoria, dysphoria, and pain, the µ-, δ-, and κ-opioid receptors and their endogenous ligands may subserve these lateralized functions. We addressed this hypothesis by comparing the levels of the opioid receptors and peptides in the left and right anterior cingulate cortex (ACC), a key area for emotion and pain processing. Opioid mRNAs and peptides and 5 "classical" neurotransmitters were analyzed in postmortem tissues from 20 human subjects. Leu-enkephalin-Arg (LER) and Met-enkephalin-Arg-Phe, preferential δ-/µ- and κ-/µ-opioid agonists, demonstrated marked lateralization to the left and right ACC, respectively. Dynorphin B (Dyn B) strongly correlated with LER in the left, but not in the right ACC suggesting different mechanisms of the conversion of this κ-opioid agonist to δ-/µ-opioid ligand in the 2 hemispheres; in the right ACC, Dyn B may be cleaved by PACE4, a proprotein convertase regulating left-right asymmetry formation. These findings suggest that region-specific lateralization of neuronal networks expressing opioid peptides underlies in part lateralization of higher functions, including positive and negative emotions and pain in the human brain.

The endogenous opioid system in human alcoholics: molecular adaptations in brain areas involved in cognitive control of addiction.

The endogenous opioid system (EOS) plays a critical role in addictive processes. Molecular dysregulations in this system may be specific for different stages of addiction cycle and neurocircuitries involved and therefore may differentially contribute to the initiation and maintenance of addiction. Here we evaluated whether the EOS is altered in brain areas involved in cognitive control of addiction including the dorsolateral prefrontal cortex (dl-PFC), orbitofrontal cortex (OFC) and hippocampus in human alcohol-dependent subjects. Levels of EOS mRNAs were measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and levels of dynorphins by radioimmunoassay (RIA) in post-mortem specimens obtained from 14 alcoholics and 14 controls. Prodynorphin mRNA and dynorphins in dl-PFC, κ-opioid receptor mRNA in OFC and dynorphins in hippocampus were up-regulated in alcoholics. No significant changes in expression of proenkephalin, and µ- and δ-opioid receptors were evident; pro-opiomelanocortin mRNA levels were below the detection limit. Activation of the κ-opioid receptor by up-regulated dynorphins in alcoholics may underlie in part neurocognitive dysfunctions relevant for addiction and disrupted inhibitory control.