Molecular electrostatic potential and pattern recognition models to design potentially active pentamidine derivatives against Trypanosoma brucei rhodesiense

Abstract

Molecular electrostatic potential (MEP) and pattern recognition (PR) were used to draw potentially active pentamidine derivatives against Trypanosome brucei rhodesiense (T. b. rhodesiense). PR models: Principal Component Analysis, PCA model; Hierarchical Cluster Analysis, HCA model; K-Nearest Neighbor, KNN model; Soft Independent Modeling of Class Analogy, SIMCA model; and Stepwise Discriminant Analysis, SDA model, were built by reducing the dimensionality of a data matrix to twenty-eight pentamidine derivatives and allowed the compounds to be classified into two classes: more active and less active, according to their degrees of activity against T. b. rhodesiense. The study outlined that the properties HOMO (highest occupied molecular orbital) energy, VOL (molecular volume), and ASA_P (water accessible surface area of all polar (½qi½³0. 2) atoms) are the most relevant for the construction of the models. The key structural features required for biological activity investigated through MEP were used as guidelines in the design of thirteen new compounds, which were evaluated by PR models as more active or less active against T. b. rhodesiense. The application of PR models indicated nine promising compounds (29, 30, 31, 32, 33, 36, 37, 39, and 40) for synthesis and biological assays.

Simple Fluorescence Sensing Approach for Selective Detection of Fe3+ Ions: Live-Cell Imaging and Logic Gate Functioning

“…Generally, the MEP surface analysis provides information regarding the three-dimensional charge distributions of molecules. When correlated with a dipole moment, partial charges, electronegativity, and chemical reactivity sites found in the molecule, MEP shows significant traits including variation in electron density, size, and form. − MEP analysis reveals the electron-rich and deficient areas of the molecules, and therefore the molecule’s sites available for the electrophilic attack can be efficiently identified by MEP analysis . This surface analysis helps to visualize differently charged regions of the molecules which are indicated by different colors.…”

Designing Artemisinins with Antimalarial Potential, Combining Molecular Electrostatic Potential, Ligand-Heme Interaction and Multivariate Models

“…Several researches carried out in this laboratory were conducted using the methods of MA mentioned in this section. Brief descriptions of these methods can be found in the articles [45] [46] [47] [48]. In this work, all MA methods were performed with the Pirouette program [49].…”