Structural Similarity Of Compounds Research Articles

Retention prediction in reversed phase high performance liquid chromatography using quantitative structure-retention relationships applied to the Hydrophobic Subtraction Model

Quantitative Structure-Retention Relationships (QSRR) methodology combined with the Hydrophobic Subtraction Model (HSM) have been utilized to accurately predict retention times for a selection of analytes on several different reversed phase liquid chromatography (RPLC) columns. This approach is designed to facilitate early prediction of co-elution of analytes, for example in pharmaceutical drug discovery applications where it is advantageous to predict whether impurities might be co-eluted with the active drug component. The QSRR model utilized VolSurf+ descriptors and a Partial Least Squares regression combined with a Genetic Algorithm (GA-PLS) to predict the solute coefficients in the HSM. It was found that only the hydrophobicity (η'H) term in the HSM was required to give the accuracy necessary to predict potential co-elution of analytes. Global QSRR models derived from all 148 compounds in the dataset were compared to QSRR models derived using a range of local modelling techniques based on clustering of compounds in the dataset by the structural similarity of compounds (as represented by the Tanimoto similarity index), physico-chemical similarity of compounds (represented by log D), the neutral, acidic, or basic nature of the compound, and the second dominant interaction between analyte and stationary phase after hydrophobicity. The global model showed reasonable prediction accuracy for retention time with errors of 30 s and less for up to 50% of modeled compounds. The local models for Tanimoto, nature of the compound and second dominant interaction approaches all exhibited prediction errors less than 30 s in retention time for nearly 70% of compounds for which models could be derived. Predicted retention times of five representative compounds on nine reversed-phase columns were compared with known experimental retention data for these columns and this comparison showed that the accuracy of the proposed modelling approach is sufficient to reliably predict the retention times of analytes based only on their chemical structures.

A Novel Bromoindole Alkaloid from a Korean Colonial TunicateDidemnumsp.

Chemical investigation on a colonial marine tunicate, Didemnum sp. led to the isolation of a series of indole alkaloids including a new (1) and two known metabolites (2-3). Based on the spectroscopic analysis including 1D and 2D NMR along with MS spectra, the structure of 1 (16-epi-18-acetyl herdmanine D) was elucidated as a new amino acid derivative. The absolute configuration of 1 was determined by comparison of specific rotation with the known compound. The structures of compounds 2 and 3 were also identified as bromoindole containing compounds N-(6-bromo-IH-indole- 3-carbonyl)-L-arginine and (6-bromo-IH-indol- 3-yl) oxoacetamide, respectively, based on 1H and 13C NMR data, MS data and specific rotation value. Their pharmacological potentials as antibacterial agents and FXR antagonists were investigated, but no significant activity was found. However, the structural similarity of compound 1 to compound 4 suggested the anti-inflammatory potential of compound 1.

Identification of Fluorescent Compounds with Non-Specific Binding Property via High Throughput Live Cell Microscopy

IntroductionCompounds exhibiting low non-specific intracellular binding or non-stickiness are concomitant with rapid clearing and in high demand for live-cell imaging assays because they allow for intracellular receptor localization with a high signal/noise ratio. The non-stickiness property is particularly important for imaging intracellular receptors due to the equilibria involved.MethodThree mammalian cell lines with diverse genetic backgrounds were used to screen a combinatorial fluorescence library via high throughput live cell microscopy for potential ligands with high in- and out-flux properties. The binding properties of ligands identified from the first screen were subsequently validated on plant root hair. A correlative analysis was then performed between each ligand and its corresponding physiochemical and structural properties.ResultsThe non-stickiness property of each ligand was quantified as a function of the temporal uptake and retention on a cell-by-cell basis. Our data shows that (i) mammalian systems can serve as a pre-screening tool for complex plant species that are not amenable to high-throughput imaging; (ii) retention and spatial localization of chemical compounds vary within and between each cell line; and (iii) the structural similarities of compounds can infer their non-specific binding properties.ConclusionWe have validated a protocol for identifying chemical compounds with non-specific binding properties that is testable across diverse species. Further analysis reveals an overlap between the non-stickiness property and the structural similarity of compounds. The net result is a more robust screening assay for identifying desirable ligands that can be used to monitor intracellular localization. Several new applications of the screening protocol and results are also presented.

Cross-enhancement of accelerated biodegradation of organophosphorus compounds in soils: Dependence on structural similarity of compounds

Rates of degradation of seven organophosphate nematicides and insecticides were examined in two soils known to show accelerated biodegradation of fenamiphos and one soil known to show accelerated biodegradation of chlorpyrifos. The results indicated that several organophosphate insecticides and one nematicide were susceptible to cross-enhanced degradation in the soil showing accelerated biodegradation of chlorpyrifos. No cross-enhancement was observed in the two soils showing accelerated degradation of fenamiphos. Fumigation resulted in the complete inhibition of pesticide degradation in all soils. The data suggested that the cross-enhancement of selected pesticides in chlorpyrifos-degrading soil was dependent on the structural similarity of the compounds. Mechanisms of degradation of pesticide in soil support this hypothesis, where structurally similar compounds (diazinon, parathion, coumaphos and isazofos) were hydrolysed by microbial activity in chlorpyrifos-degrading soil but the degradation products were accumulated. Enhanced degradation of chlorpyrifos and fenamiphos was found to be stable in the laboratory condition for a period of one year.

Isolation and structure elucidation of four new dihydro-β-agarofuran polyesters from Euonymus sachalinensis

Four new dihydro-β-agarofuran polyesters 1–4 have been isolated from the fruit of Euonymus sachalinensis(Celastraceae) and their structures elucidated by means of 1H and 13C NMR spectroscopy, including 1H–1H COSY, DEPT, 1H–13C COSY and COLOC measurements, mass spectrometry and chemical reactions. The configurations have been determined on the basis of NOESY spectra and X-ray analysis. The isolated compounds are the first native representatives of 3, 12-oxygenated dihydro-β-agarofuran in which the usual macrocycle is missing. The structural similarity of compounds 1–4 and the macrocyclic derivatives is noteworthy from a biogenetic point of view.