Synthesis and SAR comparative studies of 2-allyl-4-methoxy-1-alkoxybenzenes as 15-lipoxygenase inhibitors

A group of 2-alkoxy-5-methoxyallylbenzene were designed, synthesised and evaluated as potential inhibitors of the soybean 15-lipoxygenase (SLO) on the basis of the eugenol and esteragol structures. Compound 4d showed the best half maximal inhibitory concentration (IC??) for SLO inhibition (IC???=?5.9?±?0.6 μM). All the compounds were docked in the SLO active site retrieved from the Research Collaboratory for Structural Bioinformatics (RCSB) Protein Data Bank (PDB entry: 1IK3) and showed that the allyl group of the synthetic compounds similar to the linoleic acid double bond, were oriented toward the Fe3+-OH moiety in the active site of the enzyme and this conformation was especially fixed by the hydrophobic interaction of the 2-alkoxy group with Leu?1?, Trp?1?, Val??? and Ile??2. It was concluded that the molecular volume and shape of the alkoxy moiety was a major factor in the inhibitory potency variation of the synthetic compounds.     

Imidazolium chloride‐based ionic liquid‐assisted improvement of lipase activity in organic solvents

The activity of a lipase from a newly isolated Pseudomonas sp. was investigated in the presence of organic solvents and imidazolium chloride‐based ionic liquids (IL) such as BMIM[Cl] and HMIM[Cl]. The lipase activity in the presence of IL was higher compared to that in common organic solvents such as methanol and 2‐propanol. A possible explanation for the enzyme activation might be the structural changes induced in the protein in organic systems. Since IL quench the intensity of fluorescence emission, it was not possible to investigate the major factor that influences the enzyme behavior in these new organic salts. Furthermore, the enzyme exhibited excellent activity in buffer mixtures containing both organic solvent and IL. The stability of the lipase at 50°C was considerably increased in the presence of 20% BMIM[Cl] compared with the untreated lipase in aqueous medium. The light scattering method clearly showed that prevention of aggregation could be the reason for thermal stabilization at 50°C in reactions containing IL. Kinetic analysis of the enzyme in the presence of different concentrations of IL showed that the K_m value increased from 0.45 mM in aqueous buffer to 2.4 mM in 50% v/v BMIM[Cl]/buffer. The increase in K_m indicates that IL can significantly reduce the binding affinity of the substrate to the enzyme. Also, a linear correlation was observed between the BMIM[Cl] concentration and V_max of the enzyme. As the concentration of BMIM[Cl] increased from 10 to 50% v/v, the V_max value increased from 1.8 to 46 μM/min.     

Sources of infection in childhood tuberculosis in a region of east Croatia

Possible sources of tuberculosis (TBC) infection in children have been assessed in a retrospective epidemiological study covering a north-east region of Croatia in which the incidence of childhood tuberculosis has been increasing since the war in 1991-1995. During the past decade (1993-2003), 271 children up to 18 years of age have been referred for hospital care because of known contacts with tuberculosis (142 children, group A) or because of indicative clinical signs and symptoms (129 children, group B). Possible sources of infection were identified on the basis of medical documentation and field investigations. Frequencies of source identification for different age groups were compared. In group A, the exposure took place most often within the family (parents, grandparents, siblings, 129 of 142 children, 90.87%). Relatives, neighbors, friends and schoolmates accounted for 9.2%. In group B, possible sources of infection were identified for 44 of 129 children (34.1%) and were within the family for 16 of those 44 (36.4%). Evidenced contact with tuberculosis was more usual among younger children (0-9 years of age, 65.5%) in group A than among the older ones (10-18 years of age, 34.5%). In group B, contacts with tuberculosis were equally distributed (50.0%) among younger and older children. High proportion of unrecognized contacts in children having clinical signs and symptoms indicative of tuberculosis (group B, 85 of 129, 65.9%) opens the possibility that extra-familial exposure to tuberculosis occurs more often than expected regardless of the age of children.     

Treatment of ocular motility disturbances in Graves' disease with botulinum toxin A

The aim of this study was to evaluate the efficacy of botulinum toxin-A injections on motility disturbance in patients with dysthyroid eye disease. In 36 patients (52 orbits) with active phase of Grave's ophthalmopathy with motility disturbance, botulinum toxin-A injections were applied. Ocular motility was measured before and after treatment in four main directions (elevation, depression, abduction and adduction) with F?rster perimeter. In all patients 20 units of botulinum toxin-A in one single injection was applied in the projection of the inferior rectus muscle. Statistically, the degree of upgaze increased notably in all three groups, but mostly in the first group where it amounted up to 5.8-6.0 (z = 10.0;p = 0.68). We could not prove notable increase of the motility grade in the adduction in none of the groups of the tested patients. Due to the fact that eyeball motility can be objectively measured, effect of the applied therapy can be clearly evaluated.     

The lipogenic enzymes DGAT1, FAS, and LPL in adipose tissue: effects of obesity, insulin resistance, and TZD treatment

Acyl-coenzyme A:diacylglycerol transferase (DGAT), fatty acid synthetase (FAS), and LPL are three enzymes important in adipose tissue triglyceride accumulation. To study the relationship of DGAT1, FAS, and LPL with insulin, we examined adipose mRNA expression of these genes in subjects with a wide range of insulin sensitivity (SI). DGAT1 and FAS (but not LPL) expression were strongly correlated with SI. In addition, the expression of DGAT1 and FAS (but not LPL) were higher in normal glucose-tolerant subjects compared with subjects with impaired glucose tolerance (IGT) (P < 0.005). To study the effects of insulin sensitizers, subjects with IGT were treated with pioglitazone or metformin for 10 weeks, and lipogenic enzymes were measured in adipose tissue. After pioglitazone treatment, DGAT1 expression was increased by 33 +/- 10% (P < 0.05) and FAS expression increased by 63 +/- 8% (P < 0.05); however, LPL expression was not altered. DGAT1, FAS, and LPL mRNA expression were not significantly changed after metformin treatment. The treatment of mice with rosiglitazone also resulted in an increase in adipose expression of DGAT1 by 2- to 3-fold, as did the treatment of 3T3 F442A adipocytes in vitro with thiazolidinediones. These data support a more global concept suggesting that adipose lipid storage functions to prevent peripheral lipotoxicity.     

Dikaryotic arthroconidiation of Pleurotus subgenus Coremiopleurotus

This study was carried out to elucidate the poorly understood processes of arthroconidiation through coremium formation using Pleurotus cystidiosus subsp. abalonus. The coremia exclusively produced dikaryotic arthroconidia with the remnant of a clamp connection. Cells in the subapical zone of the hyphal bundle reduced their length by division before arthroconidiation. Approximately 400 000 arthroconidia were produced by a coremium in 1 day, with constant productivity over a 2-week period. Continuous cell extension and division in the coremium stipe supplied cells for arthroconidiation at the coremium apex, which is surrounded by a liquid droplet (coremioliquid). Maintenance of moisture with coremioliquid was necessary for arthroconidiation. The coremioliquid formation was performed by active liquid transportation in the hyphae, a process that was blocked by the microtubule depolymerization agent thiabendazole.