(E)-2-Benzylidenecyclanones: Part XIX. Reaction of (E)-2-(4'-X-Benzylidene)-1-tetralones with Cellular Thiols: Comparison of Thiol Reactivities of Open-Chain Chalcones and Their Six- and Seven-Membered Cyclic Analogs.

Non-enzyme-catalyzed thiol addition onto the α,ß-unsaturated carbonyl system is associated with several biological effects. Kinetics and diastereoselectivity of non-enzyme catalyzed nucleophilic addition of reduced glutathione (GSH) and N-acetylcysteine (NAC) to the six-membered cyclic chalcone analogs 2a and 2b were investigated at different pH values (pH 3.2, 7.4 and 8.0). The selected compounds displayed in vitro cancer cell cytotoxicity (IC50) of different orders of magnitude. The chalcones intrinsically reacted with both thiols under all incubation conditions. The initial rates and compositions of the final mixtures depended both on the substitution and the pH. The stereochemical outcome of the reactions was evaluated using high-pressure liquid chromatography with UV detection (HPLC-UV). The structures of the formed thiol-conjugates and the retro-Michael products (Z)-2a and (Z)-2b were confirmed by high-pressure liquid chromatography-mass spectrometry (HPLC-MS). Frontier molecular orbitals and the Fukui function calculations were carried out to investigate their effects on the six-membered cyclic analogs. Data were compared with those obtained with the open-chain (1) and the seven-membered (3) analogs. The observed reactivities do not directly relate to the difference in in vitro cancer cell cytotoxicity of the compounds.

Sexual dimorphism of cardiovascular ischemia susceptibility is mediated by heme oxygenase.

We investigated the gender differences in heme-oxygenase (HO) enzyme, which produces endogenous vascular protective carbon monoxide (CO). We studied (1) the activity and expression of HO enzymes in the left ventricle (LV) and aorta, (2) basal increase in basal blood pressure provoked by arginine vasopressine (AVP) in vivo, (3) the heart perfusion induced by AVP, (4) the ST segment depression provoked by adrenaline and 30 seconds later phentolamine, and (5) the aorta ring contraction induced by AVP in female and male Wistar rats. We found that HO activity and the expression of HO-1 and HO-2 were increased in female rat aorta and LV. We demonstrated that the basal blood pressure and administration of AVP provoked blood pressure response are increased in the males; the female myocardium was less sensitive towards angina. Both differences could be aggravated by the inhibition of HO. The aorta rings were more susceptible towards vasoconstriction by AVP in males; isolated heart perfusion decrease was higher in males. The HO inhibition aggravated the heart perfusion in both sexes. In conclusion, the increased HO activity and expression in females might play a role in the sexual dimorphism of cardiovascular ischemia susceptibility during the reproductive age.

Reliability of anthropometric parameters in the prediction of the visceral fat area among adult women.

Visceral fat accumulation is a risk factor for cardiometabolic diseases. Magnetic resonance imaging (MRI) and computed tomography (CT) provided the most accurate techniques of abdominal fat assessment, but these methods are very expensive. The aim of this study was to examine and compare the predictive ability of simple anthropometric parameters for visceral fat area (VFA) among adult women in different age and obesity status groups. The sample consisted of 133 adult women (aged 18-76 years). All subjects underwent anthropometric measurements. Body composition and VFA were determined with a multi-frequency bioimpedance analyzer (BIA). 16.9% of the younger women (age < 45) were obese with a body-mass index (BMI) > or = 30.0 kg/m2, and 23.2% of the older individuals (age > 45) had BMI > or = 30 kg/m2. After age and BMI adjustment, the best correlation was observed between VFA and waist circumference (WC) in younger women (R = 0.347, p = 0.002). In the case of the older women, the best correlation efficient values were for SAD (R = 0.560, p < 0.001) and hip circumference (R = 0.550, p < 0.001). The partial correlation coefficients were consistently higher for younger subjects with excessive fat accumulation (overweight & obese subgroup; individuals with WC > 80 cm) compared to women without obesity. Results of the multiple linear stepwise regression analyses showed the significance of age and BMI in prediction of VFA. In addition, hip circumference (HC) was one of the methods that best reflected VFA in older women independently from obesity status. Using single anthropometric parameters is not usually sufficient for predicting with good accuracy the VFA, but the convenient combination of these parameters could be a suitable way for the reliable prediction in Hungarian women.

In-solution and on-plate light-catalyzed E/Z isomerization of cyclic chalcone analogues. Lipophilicity of E- and Z-2-(X-benzylidene)-1-benzosuberones.

Some cyclic chalcone analogues [E-2-(X-benzylidene)-1-indanones, -tetralones, and -benzosuberones], on-plate UV light-catalyzed formation of new chromatographic spots, can be observed during thin-layer chromatography (TLC). Gas chromatographic (GC) analysis of selected derivatives indicates the formation of one new substance in each case. GC coupled with mass spectrometry and 1H NMR analysis of the samples reveals that the compounds formed are the respective Z-2-(X-benzylidene)-1-indanones, -tetralones, and -benzosuberones. Two-dimensional TLC shows that the E/Z isomerization is a reversible process. By means of the RP-TLC, the logarithm of n-octanol-water partition coefficient (log P) values of E- and Z-isomeric pairs of selected 2-(X-benzylidene)-1-benzosuberones is determined. The Z-isomers are less lipophilic than the E-isomers.

Facile synthesis of 17-formyl steroids via palladium-catalyzed homogeneous carbonylation reaction.

17-formyl-androst-16-ene and its analogues were synthesized from the corresponding 17-iodo-16-ene derivatives in palladium-catalyzed formylation reaction using tributyltin hydride as hydrogen source under mild reaction conditions. The formation of androst-16-ene and its isomerization products, as well as that of analogous steroidal olefins as side-products, was found to be dependent on the reaction conditions. The formylation reaction tolerates various functional groups on the A and B rings of the steroids.

Effect of rancid corn oil on some onco/suppressor gene expressions in vivo. A short-term study.

Autooxidation of polyunsaturated fatty acids (PUFAs) of edible oils results in the formation of fatty acid hydroperoxides that can undergo further chemical transformations to yield a variety of re-arranged and chain-cleavage products. Since the oxidation products of PUFAs have been reported to have cytotoxic and mutagenic effects, the consumption of rancid oils and fats represents a possible health hazard for the population. Storage of corn oil at room temperature and in the refrigerator for a forty-eight month period resulted in two different qualities of oil samples, which were characterized by UV, titrimetric (peroxide value, acid value) and GC-MS methods. Earlier it was demonstrated that the increase of expression of certain oncogenes and tumor suppressor genes is a method of choice for the early detection of carcinogen exposure. Treatment of CBA/Calpha inbred mice with the two oil samples showed significantly increased expression of the Ha-ras gene in all the investigated organs (liver, lung, kidney, thymus and spleen) of the rancid corn oil-treated animals. Expression of the c-myc and the p53 genes was also increased after the rancid corn oil-treatment in all the organs but the thymus of the mice. The results suggest that rancid oils, rich in omega-6 unsaturated fatty acids, could be involved not only in tumor promotion but in initiation as well.