Theoretical Studies of bioactive substances Molecular modeling and QSAR (2D and 4D) studies of: A) 1,4 Naftoquinones derivatives with Antileucemic activity. B) Herbicides 3-benzil-5-arilidenofuran-2(5H)-one and Trifluoromethyl Arylamides

Abstract

This project is divided into two main parts. In both of them, the methodologies to be used will be basically the same. 2D- and 4D-QSAR studies (studies of quantitative relationships between chemical structure and biological activity) will be developed. They vary specifically with respect to areas of application. In one case, a study of the biological activity of derivatives of 1.4-naphthoquinones with activity against leukemia will be treated in order to investigate the possible active sites and contribute to the elucidation of some details in the mechanism of action of these drugs against Leukemic cells HL-60. In another study, the herbicides 3-benzyl-5-benzilidenofuran-2 (5H)-one will be investigated. The goal in this second study is, in addition to the QSAr study, to carry out an investigation regarding the mechanism of action of such herbicides. 2D- and 4D-QSAR studies, will require calculations of descriptors based on quantum chemistry, molecular dynamics and other computational methods. The 2D QSAR analysis is performed by calculating traditional descriptors related to the hydrophobic, electronic and structural effects, such as logP, frontier orbital energies of atomic charges, dipole moment, molecular volume, surface area, among others. The electronic descriptors will be calculated with the program Gaussian03. 4D-QSAR analysis- will be performed by applying the LQTA-QSAR methodology developed in the Laboratory of Theoretical and Applied Chemometrics (LQTA) to generate field descriptors. Then regression models will be built for the two methodologies by partial least squares regression (PLS). Such models will be built and validated through the QSARmodeling program, developed in the LQTA. The two methodologies are complementary and the results will be compared at the end of the work. (AU)