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.     

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.     

Biomimetic oxidation of Hantzsch 1,4-dihydropyridines with tetra-n-butylammonium periodate catalyzed by tetraphenylporphyrinatomanganese(III) chloride [Mn(TPP)Cl

Efficient oxidation of Hantzsch 1,4-dihydropyridines to their corresponding pyridine derivatives with (Bu(4)N)IO(4) catalyzed by tetraphenylporphyrinatomanganese(III) chloride [Mn(TPP)Cl] is reported. This catalytic system shows high efficiency in the oxidation of 1,4-dihydropyridines at room temperature in the presence of imidazole.     

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.