Quantitative structure/retention relationships in affinity chromatography.

Affinity chromatography (AC) followed by quantitative structure/retention relationships (QSRR) analysis provides information on both the analytes and the macromolecules forming the stationary phases. QSRR equations derived for test series of analytes (often drugs) are interpreted in terms of structural requirements of the specific binding sites on macromolecules. Chromatographically demonstrated differences in analyte/macromolecule interactions may be relevant to molecular pharmacology and rational drug design. Multiple regression analysis of appropriately designed sets of affinity-chromatographic data may help increase the speed and efficiency of search as for new drugs and reduce the need for in vivo screening. Specific high-performance affinity-chromatographic separations can be optimized by rational selection of chiral columns, the characteristics of which are provided by QSRR.     

Predicting anti-cancer activity of quinoline derivatives: CoMFA and CoMSIA approach

The 3D quantitative structure-activity relationships of 31 quinoline nuclei containing compounds and their biological activity have been investigated to establish various models. The comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) studies resulted in reliable and significant computational models. The obtained CoMFA model showed high predictive ability with q(2) = 0.592, r(2) = 0.966 and standard error of estimation (SEE) = 0.167, explaining majority of the variance in the data with two principal components. Predictions obtained with CoMSIA steric, electrostatic, hydrophobic, hydrogen-bond acceptor and donor fields (q(2) = 0.533, r(2) = 0.985) showed high prediction ability with minimum SEE (0.111) and four principal components. The information obtained from the CoMFA and CoMSIA contour maps can be utilized for the design and development of topoisomerase-II inhibitors for synthesis.     

Pollutant Dehalogenation Capability May Depend on the Trophic Evolutionary History of the Organism: PBDEs in Freshwater Food Webs

Organohalogen compounds are some of the most notorious persistent pollutants disturbing the Earth biosphere. Although human-made, these chemicals are not completely alien to living systems. A large number of natural organohalogens, part of the secondary metabolism, are involved in chemical trophic interactions. Surprisingly, the relationship between organisms' trophic position and synthetic organohalogen biotransformation capability has not been investigated. We studied the case for polybromodiphenyl ethers (PBDE), a group of flame-retardants of widespread use in the recent years, in aquatic food webs from remote mountain lakes. These relatively simple ecosystems only receive pollution by atmospheric transport. A large predominance of the PBDE congener currently in use in Europe, BDE-209, largely dominated the PBDE composition of the basal resources of the food web. In contrast, primary consumers (herbivores and detritivores) showed a low proportion of BDE-209, and dominance of several less brominated congeners (e.g. BDE-100, BDE47). Secondary consumers (predators) showed large biomagnification of BDE-209 compare to other congeners. Finally, top predator fish characterized by low total PBDE concentrations. Examination of the bromine stable isotopic composition indicates that primary consumers showed higher PBDE biotransformation capability than secondary consumers. We suggest that the evolutionary response of primary consumers to feeding deterrents would have pre-adapted them for PBDE biotransformation. The observed few exceptions, some insect taxa, can be interpreted in the light of the trophic history of the evolutionary lineage of the organisms. Bromine isotopic composition in fish indicates that low PBDE values are due to not only biotransformation but also to some other process likely related to transport. Our finding illustrates that organohalogen compounds may strongly disturb ecosystems even at low concentrations, since the species lacking or having scarce biotransformation capability may be selectively more exposed to these halogenated hydrophobic semi-volatile organic pollutants due to their high bioaccumulation potential.