Structural invariants for the prediction of relative toxicities of polychloro dibenzo-p-dioxins and dibenzofurans.

Multivariate models are reported that can predict the relative toxicity of compounds with severe environmental impact, namely polychloro dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs). Multiple linear regression analysis (MLR) and partial least square projections of latent variables (PLS) show the usefulness of graph-theoretical descriptors, mainly topological charge indices (TCIs), in these series. The general trends of the group are correctly reproduced and better results are presented than have previously been published. In general, the more toxic compounds exhibit more symmetric molecular structures.

Comparison of the chemical composition and nutritional value of Amaranthus cruentus flour and its protein concentrate.

Plants constitute an alternative source of proteins in the human diet, with advantages over animal proteins because of their low content of saturated fats and absence of cholesterol. Within the framework of a wider research project on the role of Amaranthus cruentus (Ac) in lipid metabolism, in this work the chemical composition and biological value of the Ac flour and its protein concentrate were compared. Proximate chemical composition, amino acid and fatty acid profiles, some antinutrient factors, and biological values were determined for Ac seed flour and its protein concentrate obtained by extraction at pH 11 and precipitation at pH 4.5. The flour protein content was 16.6 g% while that of the concentrate was 52.56 g%. The content of the soluble dietary fiber with a hypolipemic function was notably higher in the protein concentrate (12.90 g%) than in the seed flour (4.29 g%). The protein concentrate also exhibited a higher content of insoluble dietary fiber. The Ac flour and the concentrate contain 75.44 and 56.95% unsaturated fatty acids, respectively. Squalene, which affects the biosynthesis of cholesterol, was detected both in the flour and the concentrate oils, with a higher content in the concentrate (9.53%) as compared to the flour (6.23%). Comparison of the amino acid composition with the FAO pattern protein indicated that the concentrate does not have limiting amino acids, while the flour has leucine, threonine, and valine. The content of lysine was high in both the flour and the concentrate, making these products particularly useful as a complement for cereal flour, which is deficient in this amino acid. The biological quality analysis demonstrated an improvement in the quality of the concentrate. The presence of saponins, phytic acid, and trypsin inhibitors in the concentrate, which favor the metabolism of lipids, suggests that consumption of the concentrate might reduce the risk of heart disease.

Simultaneous spectrophotometric determination of phenobarbital, phenytoin and methylphenobarbital in pharmaceutical preparations by using partial least-squares and principal component regression multivariate calibration.

Two multivariate calibration methods, partial least squares (PLS-2) and principal component regression (PCR) have been applied to the simultaneous spectrophotometric analysis of ternary mixtures of phenytoin (DPH), phenobarbital (PBT) and methylphenobarbital (MPBT) in the Comital-L pharmaceutical formulation. The PLS-2 and PCR procedures were employed to evaluate the data of a variable number of calibration solutions measured over the wavelength range 400-700 nm. The concentration ranges used to construct the calibration matrix were varied between 5 and 30 microg ml(-1). The proposed methods were validated by applying them to the analysis of the Comital-L pharmaceutical formulation and the average relative errors were less than 6% for each one of the analyzed compounds. The results obtained by both proposed methods have been compared with the results obtained by application of a RPLC reference method.

Structure-antifeedant activity relationship of clerodane diterpenoids. Comparative study with withanolides and azadirachtin.

A structure-antifeedant activity relationship (SAR) study of clerodane diterpenoids was carried out. Attention was focused on the feeding-deterrent activities exhibited toward Tenebrio molitor by clerodane diterpenoids and withanolides. Azadirachtin was chosen as a reference compound. SAR studies on the clerodane compounds indicate that the stereoelectronic factors are more important than the hydrophobic aspects as determinants of antifeedant activity. A furan ring in the side chain and a carbonyl alpha,beta-unsaturated (or spiro-epoxide) group appear to be indispensable for the biological response. A conformational study indicate that the optimum interatomic distance between these moieties is a range between 9.5 and 10.5 A. In addition, a similar stereoelectronic response was found among withanolides and azadirachtin. On the basis of these results it is reasonable to imagine a closely related chemical mechanism for these compounds.

Simultaneous spectrophotometric determination of La, Ho, Mn 5-Br-PADAP complexes using multivariate calibration with partial least-squares (PLS) data evaluation.

A simple and fast analytical pocedure is proposed for the simultaneous spectrophotometric determination of lanthanum, holmium and manganese in synthetic ceramics, (La(0.8-x) Hox Sr0.2 MnO3), by using the partial least-squares (PLS) method. As chromogenic agent 5-Br-PADAP [2-(5-bromo-2-pyridylazo)-5-diethylaminophenol] was used, which form colored complexes with the three elements studied. To avoid metal hydrolysis, a mixture of ethanol and Triton X-100 at pH 9.5 was used for all experiments. A set of 17 calibration solutions measured throughout the 400-700 nm wavelength range was used in the calibration step. The concentration range for Mn(II) was 1-12 x 10(-6) mol L-1, while the range for the rare earth elements La(III) and Ho(III) was 2-8 x 10(-6) mol L-1. In order to demonstrate the applicability of the proposed method, a set of artificial samples containing the three analytes in variable proportions was prepared and analyzed. The analytical results obtained were quite acceptable with relative errors not greater than 7% in most cases.

Prediction of the brain-blood distribution of a large set of drugs from structurally derived descriptors using partial least-squares (PLS) modeling.

In this study, the multivariate partial least-squares projections to latent structures (PLS) technique was used for modeling the brain-blood concentration ratio (BB) of 61 structurally diverse compounds. The PLS model was based on molecular descriptors that can be calculated for any compound simply from a knowledge of its molecular structure, and the model included several topological and constitutional descriptors. The PLS analysis resulted in a significant three-component model with the following statistics: r = 0.922, Q = 0.867, s = 0.318, n = 58, and F = 102. The predictive ability of the model was assessed by means of crossvalidation and also by using BB partitioning data, BBB permeability data, and 1 set of qualitative brain penetration data, resulting in BB distribution data for 97 compounds. The results indicate that the PLS model developed is statistically sound and is sufficiently robust for predictive use. Taking into account the great ease of computation and interpretation of the derived model, it may be of general utility in predicting BB ratios for a very wide range of new drugs.

QSAR based on multiple linear regression and PLS methods for the anti-HIV activity of a large group of HEPT derivatives.

Quantitative structure-activity relationships have been developed for a set of 107 inhibitors of the HIV-1 reverse transcriptase, derivatives of a recently reported HIV-1 specific lead: 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT). The activity of these compounds was investigated by means of multiple linear regression (MLR) and PLS regression techniques and topological indexes as well as several tabulated physicochemical substituent constants were used as predictor variables. The results obtained indicate that the anti-HIV activity of the HEPT derivatives is strongly dependent on hydrophobic factors as expressed by the Hansch constant (sigma pi (R1+R2)), and especially dependent on the geometric factors mainly accounted for by the 1 chi N (R2) and 4 chi pN molecular connectivity indexes and also for the molecular volume (Vx), the Taft steric constant (Es(2R1)), and the Verloop parameter for the smallest width value (B1(3R1)). Besides, for this data set, comparison of the quality of MLR and PLS models show that PLS is a better approach to MLR for improving the interpretability of the data and also to exhibit models with a better predictive quality.

Molecular topology and quantum chemical descriptors in the study of reversed-phase liquid chromatography. Hydrogen-bonding behavior of chalcones and flavanones.

The reversed-phase liquid chromatographic hydrophobicity parameters (log K'w and S) of several chalcones and flavanones were determined with methanol:water mobile phases of different compositions and with trace quantities of n-decylamine and 1-octanol added to the eluent to minimize the silanophilic interactions present in alkylsilane-bonded phases. It has been reported that qualitative hydrogen bonding information can be obtained from the relationship between S and log K'w determined with these chromatographic conditions. To quantitatively describe the hydrogen-bonding discrimination effects observed for the compounds under study, the parameter delta was defined as follows: delta(s-log kw) = S-log K'w. With topological and molecular orbital calculations, several molecular descriptors were computed for test compounds, and multivariate statistical techniques were used to examine the informative value of the parameter proposed. The results obtained indicate that delta(s-log Kw) encodes structural information mainly related to the molecular polarity and the ability of compounds to participate in hydrogen-bonding interactions. Similar structural information was also obtained for delta(s-log Kw) values of 31 structurally dissimilar compounds.

[Mountain chinchilla (Lagostomus maximus maximus Blainv) meat. Biological value]. / Carne de vizcacha (Lagostomus maximus maximus Blainv). Valor biológico.

In order to establish the vizcacha meat quality as food, the percentual chemical composition, cholesterol content and values of some fatty acids were determined. Assays were performed using Wistar rats for estimation of Net Protein Utilization (UPN), True Digestibility (TD) and Biological Value (BV). The results obtained were: protein, 23.87 g/100 g; total lipids, 3.74g/100g and a low content of cholesterol of 50 mg/100g. From the analysis of the fatty acids composition it is noticed a remarkable high proportion of insatured C18 fatty acids. The nitrogen availability calculated from UPN studies gave a value of 60.50 +/- 9.7, a TD of 85.00 +/- 13.20 and a BV of 70.60. Considering on the whole the results here obtained and the optimal approval of this product by man, it is inferred that vizcacha meat constitutes a good base for the production of foods suitable to be manufactured as can products. An adequate promotion of this product will be needed for its introduction in new markets.