Bioactive Xanthone C-glycoside Derivatives – QSAR Approach

Abstract

Introduction. Xanthone glycosides have unique structures and properties. Many efforts focus on the search for C-glycoside derivatives of mangiferin with higher bioavailability. The application of the QSAR approach allows for the optimization of the search for novel xanthone derivatives with the desired characteristics. Aim. Using available descriptors of chemical structure, physical-chemical properties, and biological activity, analyze a sample set of known homologs and analogs of mangiferin to QSAR prognosis bioactivity of new xanthone C-glycosides. Materials and methods. 26 molecules of natural homologs and modified derivatives of mangiferin formed the analyzed sample set. Topological graphs of compounds were constructed using ChemicPen software. ChemicDescript software was used for the calculation of molecular descriptors, including the Balaban index. Physicochemical characteristics of molecules as well as Lipinski's rule criteria were calculated in Molinspiration. The spectrum of the most probable ( P a > 0.7) biological activity of the described compounds were predicted using Pass Online. The software Origin (OriginLab, USA) was used for the graphical representation of the results. Results and discussion. Mangiferin and its natural homologs are the most hydrophilic compounds. The hydrolysis of the C-glycosidic bond, alkylation, acylation, and the introduction of an amino substituent radical into the mangiferin structure led to the increase of its lipophilic properties. The spectrum of the most probable biological activities of the described molecules: antitumor, antioxidant, and cardioprotective effects. The results of ADMET modeling based on the substance-drug similarity criteria showed that only 4 compounds correspond to the rule of five. We proposed the validation model to predict bioactivity from lipophilicity and molecule structure described with Balaban index. The error of prediction obtained in a result of cross-validation turned out to be about less than 3 %. Conclusion. A correlation between the structure and properties of the molecules discussed has been demonstrated. The obtained results can be used for further prediction of the properties of natural and synthetic xanthone C-glycosides and directed synthesis of new active compounds.