Year-end Sale % OFF 
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.
Highlights
Human African Trypanosomiasis (HAT) is endemic in 36 sub-Saharan countries: 24 of them experience Trypanosoma brucei gambienese (T. b. gambiense) transmission, leading to West African sleeping sickness, while in 13 countries Trypanosoma brucei rhodesiense (T. b. rhodesiense) is present, causing the most acute East African sleeping sickness syndrome, Uganda being the only country reporting both types (WHO, 2019; Selby, et al, 2019)
We present a study of the application of Molecular electrostatic potential (MEP) and pattern recognition (PR) models for the investigation of pentamidine and derivatives with activity against T. b. rhodesiense reported in literature (Bakunova, et al, 2009), and the designing of new potentially active derivatives
2.1 Molecular Electrostatic Potential in the Ligand-Receptor Biological Process MEP is a very useful topological index in the study of hydrogen bond interactions as well as in the understanding of electrophilic and nucleophilic attack sites in a molecule obtained from electron density (Scrocco & Tomasi, 1979; Politzer & Murray, 2021)
Summary
Human African Trypanosomiasis (HAT) is endemic in 36 sub-Saharan countries: 24 of them experience Trypanosoma brucei gambienese (T. b. gambiense) transmission, leading to West African sleeping sickness, while in 13 countries Trypanosoma brucei rhodesiense (T. b. rhodesiense) is present, causing the most acute East African sleeping sickness syndrome, Uganda being the only country reporting both types (WHO, 2019; Selby, et al, 2019). The MEP (Bernardinelli, et al, 1994; Jefford, et al, 2000) and PR (Gangwal, et al, 2016) approaches have been used as independent strategies in the study of active compounds and in proposing new molecules for synthesis and biological testing (Bernardinelli, et al, 1994; Gangwal, et al, 2016) The combination of these two powerful tools to unravel the structure-activity relationship of bioactive compounds and, propose new molecules was shown by our research group on the designing of potentially active compounds against human hepatocellular carcinoma HepG2, Plasmodium falciparum, and Trypanosoma cruzi, respectively (Barbosa, et al, 2011; Cristino, et al, 2012; Santos, et al, 2020)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
