IMMOBILIZED ARTIFICIAL MEMBRANE CHROMATOGRAPHY OF SUBSTITUTED CHALCONES AND CORRELATION WITH BACTERIOSTATIC ACTIVITY

TALIA, J.M.; NIETO VAZQUEZ, M.; RAMIREZ, DANIELA; LUCO, JUAN

Otro; XXXVI Scientific Meeting of the Cuyo Biology Society; 2018

The high performance liquid chromatography (HPLC) on a stationary phase composed of phospholipids, the so called immobilized artificial membrane (IAM), has been widely recognized as a valuable alternative method to extract and quantify information about the structure and physicochemical properties of organic compounds, particularly hydrophobicity parameters that are extensively used in studies of quantitative structure-activity relationships (QSAR). In the present study, the chromatographic capacity factors (log k(IAM)) for 19 natural and synthetic substituted chalcones were determined by IAM-HPLC. In order to evaluate the ability of the IAM phase in assessing lipophilicity of the compounds under study, it was of interest to study to what extent the log k(IAM) values were related to the octanol-water partition coefficients (CLOGP) values. Because a moderate correlation was found between log k(IAM) and CLOGP values, several quantitative structure-retention relationships (QSRR) were derived to explore fundamental intermolecular interactions that govern the retention of compounds under study on the IAM phases. Thus, the multiple linear regression (MLR) technique was used for modeling the IAM-chromatographic data determined for these compounds, and the molecular characterization was carried out by calculating several nonempirical descriptors which were subsequently used in the construction of QSRR models. The selected MLR-model for all compounds (n=19), which was highly significant statistically, was as follows: log k(IAM) = - 4,34 + 0,298 CLOGP + 0,135 PCWTe + 16,5 RNCG (r = 0.953, r(pred) = 0.943, s = 0.05 and F = 48.6). From the analysis of the obtained results, it can be inferred that, as expected, the hydrophobic factors are of prime importance for the IAM-retention of these compounds, but the specific polar interactions such as expressed by charge descriptors (PCWTe, RNCG) are also involved. On the other hand, in the present work we also attempted to evaluate the ability of the IAM phase in assessing the antimicrobial activity of chalcones under study. Thus, the bacteriostatic activities exerted by a subset of 11of these compounds against Staphylococcus aureus ATC25923 strains, were investigated by means of QSAR modeling and by using the partial least squares (PLS) approach. The PLS analysis of minimal inhibitory concentrations (MICs) data for the 11 chalcones tested, yielded a two-component PLS model with the following statistics: R2 = 0.984, R2(pred) = 0.890 and F = 254.5. From the analysis of the obtained results, it may be concluded that the bacteriostatic activity of the chalcones under study is strongly dependent on hydrophobic factors as expressed by log k(IAM), and especially dependent on the geometric factors mainly accounted for by the directional and three-dimensional WHIM descriptors (G3u, E1m and E3m), which encode the influence of the different aspects of the molecular shape. In conclusion, the present work provides evidence for the great potential of the IAM phases in the development of QSAR models.