Four enantiomerically pure (S)-4-alkylthioamphetamine derivatives were evaluated as monoamine oxidase (MAO) inhibitors using the human and rat isoforms of the enzyme. Molecular dockings were performed in order to gain insights regarding the binding mode of these inhibitors. All compounds were potent and selective MAO-A inhibitors although different rank orders of potencies were observed against the enzymes from different species. This behavior can be rationalized on the basis of different binding modes to each enzyme, as determined in silico. These findings further support the concept that MAO inhibitory activity of novel compounds, determined with enzymes from diverse mammalian species, should be considered with caution if human MAO is the final target to be addressed.

It was synthesized nine polyoxygenated chalcones with a potential and safe use as antioxidant, antimicrobial and anti-inflammatory therapies. Chalcones obtained by Claisen-Schmidt condensation were studied as antioxidant, inhibitors of human 5-lipoxygenase, antifungal, antibacterial and antibiotic resistance modifiers. Two chalcones with catecholic moieties were able to strongly decrease the minimum inhibitory concentration (MIC) of methicillin against methicillin-resistant Staphylococcus aureus, increase the antiradical activity and significantly inhibit the human 5-lipoxygenase. Only one of these chalcones was active synergistically with methicillin. Chalcones with methoxyl substituents at different positions displayed the best activities against Cryptococcus neoformans. Only one chalcone showed good activity against the plant pathogenic bacteria Pseudomonas syringae whose half maximal inhibitory concentration (IC 50) value (2.5 µg mL-1) was similar to that observed with the antibiotic streptomycin (2.9 µg mL-1). These simple chalcones have safe potential uses in antioxidant, antimicrobial and anti-inflammatory therapies.

The synthesis of twenty six prenylated phenols derivatives is reported. These compounds were obtained under mild conditions via Electrophilic Aromatic Substitution (EAS) coupling reactions between phenol derivatives containing electron-donor subtituents and 3-methyl-2-buten-1-ol using BF3·OEt2. Dialkylations were also produced with this method. The formation of a chroman ring by intramolecular cyclization between a sp2 carbon from the prenyl group with the hydroxyl substituent in the ortho position occurred with some phenols. All the synthesized compounds were evaluated as antioxidants according to a DPPH radical scavenging activity assay. IC50 values of five synthesized compounds indicated they were as good antioxidants as Trolox™.

The known geranylhydroquinone 2, geranylorcinol 4 and the derivative (E)-4-(3,7-dimethylocta-2,6-dienyl)-5-methylbenzene-1,3-diol 5, were prepared by Electrophilic Aromatic Substitution (EAS) reactions between the corresponding phenol derivatives containing electron-donor subtituents and geraniol using BF 3 ×OEt 2 as a catalyst. In addition, spectroscopic NMR information for 4 and 5 is complemented. Furthermore, the new (E)-2-(3,7-dimethylocta-2,6-dienyl) benzene-1,3,5-triol (geranylphloroglucinol) 13, (E)-2-(3,7-dimethylocta-2,6-dienyl)-1,3,5-trimethoxybenzene 14, (E)-2-(3,7-dimethylocta-2,6-dienyl)-6-methoxyphenol 15, (E)-3-(3,7-dimethylocta-2,6-dienyl)-2-methoxyphenol 16, (E)-5-(3,7-dimethylocta-2,6-dienyl)-2-methoxyphenol 17, (E)-4-(3,7-dimethylocta-2,6-dienyl)benzene-1,3-diol 18, (E)-3-(3,7-dimethylocta-2,6-dienyl)benzene-1,2-diol 19, (E)-4-(3,7-dimethylocta-2,6-dienyl)-5-isopropyl-2-methylphenol 20, (E)-2-(3,7-dimethylocta-2,6-dienyl)-4-isopropyl-3-methylphenol 21, (E)-2-(3,7-dimethylocta-2,6-dienyl)-4-isopropyl-5-methylphenol 22, and(E)-2-tert-butyl-4-(3,7-dimethylocta-2,6-dienyl)-5-methylphenol 23 were also prepared with this synthesis strategy. All the synthesized compounds were fully characterized and their structures were established by IR, MS and mainly NMR spectroscopic dates.

Premature rupture of chorioamniotic membranes complicated with intrauterine infection has been associated to degradation of extracellular matrix (ECM), which could explain local morphological changes. We used a culture system in which the chorioamniotic membranes form two independent chambers, allowing for the selective stimulation of either the amnion (AMN) and/or the choriodecidua (CHD) regions. Lipopolysaccharide (500 ng/ml) was added to the AMN and/or the CHD; secretions and gelatinolytic activity of matrix metalloproteinase (MMP)-2 and MMP-9 were measured in both compartments by enzyme-linked immunosorbent assay (ELISA) and zymography. Secretions of TIMP-1, TIMP-2 and TIMP-4 were measured by ELISA. Both metalloproteinases were immunolocalized in tissue sections. All stimulation modalities induced a similar proMMP-2 and proMMP-9 secretion pattern in the CHD with concentrations of 2.49 ng/ml and 90.91 pg/ml, respectively; the AMN showed no significant changes. The active forms of both enzymes did not change with any stimulation modality. TIMP-1, TIMP-2 and TIMP-4 secretions remained without significant changes (P = 0.41). ECM degradation and structural disarrangement were evident after stimulation. Secretion of proMMP-2 and proMMP-9 mainly in the CHD, presence of active forms associated to the tissue and minor changes in TIMPs secretion could favor ECM degradation and explain the weakening and thinning associated with the pathological rupture of chorioamniotic membranes.