Next Article in Journal
Path Integral Calculation of the Hydrogen/Deuterium Kinetic Isotope Effect in Monoamine Oxidase A-Catalyzed Decomposition of Benzylamine
Previous Article in Journal
Thiyl Radical Reactions in the Chemical Degradation of Pharmaceutical Proteins
Previous Article in Special Issue
Lipophilicity Determination of Antifungal Isoxazolo[3,4-b]pyridin-3(1H)-ones and Their N1-Substituted Derivatives with Chromatographic and Computational Methods
Open AccessArticle

A Comprehensive QSAR Study on Antileishmanial and Antitrypanosomal Cinnamate Ester Analogues

Institut für Pharmazeutische Biologie und Phytochemie (IPBP), Westfälische Wilhelms Universität-Münster, PharmaCampus-Corrensstraße 48, D-48149 Münster, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Julio Caballero
Molecules 2019, 24(23), 4358; https://doi.org/10.3390/molecules24234358
Received: 11 November 2019 / Revised: 22 November 2019 / Accepted: 26 November 2019 / Published: 28 November 2019
(This article belongs to the Special Issue Computational Methods for Drug Discovery and Design)
Parasitic infections like leishmaniasis and trypanosomiasis remain as a worldwide concern to public health. Improvement of the currently available drug discovery pipelines for those diseases is therefore mandatory. We have recently reported on the antileishmanial and antitrypanosomal activity of a set of cinnamate esters where we identified several compounds with interesting activity against L. donovani and T. brucei rhodesiense. For a better understanding of such compounds’ anti-infective activity, analyses of the underlying structure-activity relationships, especially from a quantitative point of view, would be a prerequisite for rational further development of such compounds. Thus, quantitative structure-activity relationships (QSAR) modeling for the mentioned set of compounds and their antileishmanial and antitrypanosomal activity was performed using a genetic algorithm as main variable selection tool and multiple linear regression as statistical analysis. Changes in the composition of the training/test sets were evaluated (two randomly selected and one by Kennard-Stone algorithm). The effect of the size of the models (number of descriptors) was also investigated. The quality of all resulting models was assessed by a variety of validation parameters. The models were ranked by newly introduced scoring functions accounting for the fulfillment of each of the validation criteria evaluated. The test sets were effectively within the applicability domain of the best models, which demonstrated high robustness. Detailed analysis of the molecular descriptors involved in those models revealed strong dependence of activity on the number and type of polar atoms, which affect the hydrophobic/hydrophilic properties causing a prominent influence on the investigated biological activities. View Full-Text
Keywords: cinnamate ester analogues; QSAR; leishmaniasis; human african trypanosomasis; validation; MLR; OPLS. cinnamate ester analogues; QSAR; leishmaniasis; human african trypanosomasis; validation; MLR; OPLS.
Show Figures

Graphical abstract

MDPI and ACS Style

Bernal, F.A.; Schmidt, T.J. A Comprehensive QSAR Study on Antileishmanial and Antitrypanosomal Cinnamate Ester Analogues. Molecules 2019, 24, 4358.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop