Estudo da relação estrutura atividade de chalconas com atividade anti-tumoral

Abstract

Plant Kingdom is an important source of compounds useful for the treatment of diseases, being used as a source of compounds with drug potential. One of these substances that is extensively studied are the chalcones, due to the fact that it has a simple structure and wide range of pharmacological applications. One possible application of the chalcones is as antitumor agents, that because of their structural similarity with combretastatins group of substances widely used as antimitotic agents that act by inhibiting tubulin polymerization, preventing mitotic spindle formation of cancer cells. Because of this similarity, Chaconas derivatives were synthesized by our research group and its activities were tested against cancer cells HCT-8 and type MDAMB-435. Been proposed the study of the structure activity with the aim to propose mathematical models to characterize the structural or physicochemical aspects that are important for biological activity. The structures of 25 analogues of chalcones had their structures optimized using the software HyperChem 8.0 Realese and Gaussian 03, based on semi-empirical methods, AM1 and ab initio method, based on the Density Functional Theory, based on the functional theory of correlation hybrid B3LYP with the combination of basis functions 6-31**, to obtain the geometric descriptors such as the length of the bonds, angles between atoms and dihedral angles, and physico-chemical as coefficient partition, dipolo moment, mass, energy of HOMO, LUMO, among others. With these calculated descriptors, the selection of mainly descriptors for each relevant biological activity was made, through the Fisher’s weight and the algorithm of successive projections, selecting the best model using multi-linear regressions. The selected models showed coefficients of determination for activity against the line cells HCT-8 with value of R2 = 0.784, and for activity against strain MDAMB-435 value of R2 = 0,741, being possible propose functions with high sensitivity and selectivity identified by confusion matrix. From From these results proved the importance of the angle of the aromatic rings in biological activity being due to stereo impediment or by hydrophobic interactions or induced dipole with ionized amino acid residues.