A Computer-Based Approach to the Rational Discovery of New Trichomonacidal Drugs by Atom-Type Linear Indices

Abstract

Computational approaches are developed to design or rationally select, from structural databases, new lead trichomonacidal compounds. First, a data set of 111 compounds was split (design) into training and predicting series using hierarchical and partitional cluster analyses. Later, two discriminant functions were derived with the use of non-stochastic and stochastic atom-type linear indices. The obtained LDA (linear discrimination analysis)-based QSAR (quantitative structure-activity relationship) models, using non-stochastic and stochastic descriptors were able to classify correctly 95.56% (90.48%) and 91.11% (85.71%) of the compounds in training (test) sets, respectively. The result of predictions on the 10% full-out cross-validation test also evidenced the quality (robustness, stability and predictive power) of the obtained models. These models were orthogonalized using the Randic orthogonalization procedure. Afterwards, a simulation experiment of virtual screening was conducted to test the possibilities of the classification models developed here in detecting antitrichomonal chemicals of diverse chemical structures. In this sense, the 100.00% and 77.77% of the screened compounds were detected by the LDA-based QSAR models (Eq. 13 and Eq. 14, correspondingly) as trichomonacidal. Finally, new lead trichomonacidals were discovered by prediction of their antirichomonal activity with obtained models. The most of tested chemicals exhibit the predicted antitrichomonal effect in the performed ligand-based virtual screening, yielding an accuracy of the 90.48% (19/21). These results support a role for TOMOCOMD-CARDD descriptors in the biosilico discovery of new compounds.

Antichagasic, Leishmanicidal, and Trichomonacidal Activity of 2‐Benzyl‐5‐nitroindazole‐Derived Amines

“…Both are generally effective, but alternatives should be sought to treat those patients who are hypersensitive and the infections caused by nitroimidazoles‐resistant isolates . In this regard, the trichomonicidal activity of various 5‐nitroindazole derivatives such as 3‐alkoxy‐1‐ and 2‐alkylindazoles, 3‐alkoxyindazoles, 1‐substituted indazol‐3‐ols, and 2‐substituted and fused indazolin‐3‐ones has recently been described.…”

Estimation of ADME Properties in Drug Discovery: Predicting Caco-2 Cell Permeability Using Atom-Based Stochastic and Non-stochastic Linear Indices

“…In the present report, we outline salient features concerned with only one of these subprograms, CARDD, and with the calculation of non‐stochastic and stochastic atom‐based linear indices, considering and not considering H‐atoms in the molecular pseudograph (G). The total and local linear indices for small‐to‐medium‐sized organic compounds have been explained in some detail in the literature 40–46. However, as Supplemental Material we give an example of differences between non‐stochastic and stochastic liner indices.…”

A successful virtual screening application: prediction of anticonvulsant activity in MES test of widely used pharmaceutical and food preservatives methylparaben and propylparaben

“…In regression analysis, however, the dependent variable is a continuous quantity while for LDA it is a categorical variable (the class label). Linear discriminant analysis has been applied extensively in drug discovery [10][11][12][13]. Our group has also applied this methodology in the identification of new antichagasic and anticonvulsant agents [14][15][16], recently reporting the anticonvulsant activity of abietic acid [16].…”