Iodine nutritional status in pregnant women of two historically different iodine-deficient areas of Catalonia, Spain.

OBJECTIVE: Catalonia (Spain) has a historically worse situation of mild iodine deficiency in the Pyrenees Mountains compared with the coastal region. The aim of this study was to evaluate the current iodine status in pregnant women living in these two areas. METHODS: An epidemiologic prospective survey included 267 consecutive pregnancies in the Catalan mountains (n = 139) and coast (n = 128) studied during the first trimester; an additional subset of 135 women from the initial cohort was available for evaluation in the third trimester. Urinary iodine (UI) was measured, and questionnaires to determine iodized salt and sea fish consumption and potassium iodide supplementation were administered. RESULTS: The median UI in the first trimester was 163 µg/L for the entire cohort, with differences between mountain and coastal regions (209 versus 142 µg/L, P = 0.007). The highest prevalence of iodized salt consumption was in the mountain area (58% versus 36.4%, P < 0.001). For the entire group, a higher median UI was found in iodized salt consumers compared with non-consumers (193 versus 134 µg/L, P < 0.001). In the third trimester, an increase of median UI was seen in those to whom iodine supplements were given during pregnancy (190 versus 154 µg/L, P = 0.015). CONCLUSION: A reversal in the historically iodine-deficient situation was observed in the Catalan Pyrenees compared with the coastal area, with a globally acceptable iodine status in pregnant women of the two geographic locations. Iodized salt consumption seems to have contributed to maintaining an acceptable iodine status in this population.

Synthesis, SAR and antibacterial studies on novel chalcone oxazolidinone hybrids.

With an intention to synergise the antibacterial activity of chalcones and oxazolidinones, several hybrid compounds possessing both chalcone and oxazolidinone moieties were synthesized and tested for antibacterial activity. The hybrid molecules containing heterocycles instead of aromatic ring were found to be active. A SAR study with various heterocycles resulted in a lead molecule 20, which was converted to one of the potent antibacterial compounds 27.

Synthesis of novel tricyclic oxazolidinones by a tandem SN2 and SNAr reaction: SAR studies on conformationally constrained analogues of Linezolid.

A series of conformationally constrained analogues of Linezolid were synthesised by employing a tandem SN(2) and SNAr reaction as the key step and tested for antibacterial activity. While the hexahydroazolo-quinoxaline compounds were inactive, the tetrahydroazolo-benzothiazine compounds exhibited interesting antibacterial activity. The introduction of fluorine in the aromatic ring further made the compounds more potent in acetamide compounds resulting in an interesting analogue 32. However, the introduction of fluorine (analogue 34) on the already potent non-fluorine thiocarbamate 21 did not have any influence on the activity.

Synthesis and antibacterial activity of novel oxazolidinones bearing N-hydroxyacetamidine substituent.

Novel oxazolidinone antibacterials containing N-hydroxyacetamidine moiety are synthesized with the diversity at C-5 terminus. These compounds have been evaluated against a panel of clinically relevant gram-positive and gram-negative pathogens. Most of the analogs in this series displayed activity superior to Linezolid and in vivo efficacies of selected oxazolidinones are also disclosed herein.

Effects of positional and geometrical isomerism on the biological activity of some novel oxazolidinones.

Some novel oxazolidinone derivatives with benzotriazole as pendant have been synthesized and tested for antibacterial activity. Linearly attached benzotriazole derivative showed more potency compared to angular one in vitro. Out of E/Z-isomers of angularly attached derivatives E-isomer was found to be more potent than Z-isomer. Either less active or inactive molecules were obtained, when benzotriazole was replaced with benzimidazole, benzthiazole, or benzoxazole. Finally, thioacetamide analogue of linear compound gave a lead having activity similar to linezolid in vitro.

Influence of ethylene-oxy spacer group on the activity of linezolid: synthesis of potent antibacterials possessing a thiocarbonyl group.

The influence of an ethylene-oxy spacer element between the heterocycle and the aromatic ring in linezolid is reported. The introduction of such spacer group generated compounds with inferior antibacterial activity. However, the conversion of the acetamide group present in the linezolid analogues to either thiocarbamate or thioacetamide functionality restored the activity. The synthesis of linezolid analogues possessing the ethylene-oxy spacer group along with SAR studies with different heterocycles and preparation of some thiocarbonyl compounds possessing potent antibacterial property are presented.

Origin of 1,3-induction in the addition of alkyl lithium to imines bearing an N-stereogenic center.

The origin of diastereoselectivity in the addition of alkyl lithium to chiral Schiff bases has been investigated experimentally and theoretically and the formation of the major diastereomer can be explained from the energy minimized structure of the Schiff base in which the phenyl group has been found to orient in such a manner that it posed lesser steric hindrance to the incoming nucleophile as compared to the alkyl group.

Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of tricyclic oxazolidinones as antibacterial agents.

Oxazolidinones exemplified by eprezolid and linezolid are a new class of antibacterials that are active against Gram positive and anaerobic bacteria including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE) and vancomycin resistant enterococci (VRE). In an effort to have a better antibacterial agent in the oxazolidinone class, we have performed three-dimensional quantitative structure-activity relationship (3D-QSAR) studies for a series of tricyclic oxazolidinones. 3D-QSAR studies were performed using the Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) procedures. These studies were performed using 42 compounds; the QSAR model was developed using a training set of 33 compounds. The predictive ability of the QSAR model was assessed using a test set of 9 compounds. The predictive 3D-QSAR models have conventional r(2) values of 0.975 and 0.940 for CoMFA and CoMSIA respectively; similarly, cross-validated coefficient q(2) values of 0.523 and 0.557 for CoMFA and CoMSIA, respectively, were obtained. The CoMFA 3D-QSAR model performed better than the CoMSIA model.

Highly efficient CuI-catalyzed coupling of aryl bromides with oxazolidinones using Buchwald's protocol: a short route to linezolid and toloxatone.

[reaction: see text] Coupling of a variety of substituted aryl bromides with oxazolidinones has been achieved using the Buchwald protocol for the amidation of aryl halides. This procedure is exemplified by the synthesis of two medicinally important molecules, linezolid and toloxatone.