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

• Autor(a) principal: Oliveira, Luã Felipe Souza de
• Data de Publicação: 2021
• Outros Autores: Cordeiro, Hérica Coelho, Brito, Helieverton Geraldo de, Pinheiro, Ana Cecília Barbosa, Santos, Marcos Antonio Barros dos, Bitencourt, Heriberto Rodrigues, Figueiredo, Antonio Florêncio de, Araújo, Josué de Jesus Oliveira, Gil, Fábio dos Santos, Farias, Márcio de Souza, Barbosa, Jardel Pinto, Pinheiro, José Ciríaco
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Research, Society and Development
• Texto Completo: https://rsdjournal.org/index.php/rsd/article/view/20207
• topic: Molecular electrostatic potential; Pattern recognition models; Investigation of pentamidine derivatives; Design of pentamidine derivatives.; Potencial electrostático molecular; Modelos de reconocimiento de patrones; Investigación de derivados de pentamidina; Diseño de derivados de pentamidina.; Potencial eletrostático molecular; Modelos de reconhecimento de padrões; Investigação de derivados da pentamidina; Desenho de derivados da pentamidina.

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.