The conformation-independent QSPR approach for predicting the oxidation rate constant of water micropollutants

In advanced water treatment processes, the degradation efficiency of contaminants depends on the reactivity of the hydroxyl radical toward a target micropollutant. The present study predicts the hydroxyl radical rate constant in water (kOH) for 118 emerging micropollutants, by means of quantitative structure-property relationships (QSPR). The conformation-independent QSPR approach is employed, together with a large number of 15,251 molecular descriptors derived with the PaDEL, Epi Suite, and Mold2 freewares. The best multivariable linear regression (MLR) models are found with the replacement method variable subset selection technique. The proposed five-descriptor model has the following statistics for the training set: R2 train = 0:88, RMStrain = 0.21, while for the test set is R2 test = 0:87, RMStest = 0.11. This QSPR serves as a rational guide for predicting oxidation processes of micropollutants.Instituto de Investigaciones Fisicoquímicas Teóricas y AplicadasFacultad de Ciencias Agrarias y Forestale

QSAR predictions on antichagas fenarimols

A useful QSAR model was developed to predict the antichagas activity for 760 fenarimol analogues obtained from the ChEMBL database, which are considered as very active and selective inhibitors of Trypanosoma cruzi. Various molecular descriptor programs provided a large number of 67,116 non-conformational molecular descriptors that were analyzed through multivariable linear regressions and the Replacement Method technique. Through THESE descriptors, the quantification of the structure–activity relationship achieves an acceptable statistical quality for compounds having experimental activity. The present work provides a prospective guide for predicting the inhibitory activity against T. cruzi of structurally-related fenarimol compounds.Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicada

Conformation-Independent QSAR Study on Human Epidermal Growth Factor Receptor-2 (HER2) Inhibitors

Inhibition of HER2 (human epidermal growth factor receptor 2) expression and function is required in several cancer treatments. Numerous compounds with very different molecular structures have been suggested as HER2 inhibitors. Here we perform quantitative structure-activity relationship (QSAR) analysis on 444 of such compounds to investigate the molecular properties that may influence its efficiency. Models based on 1D and 2D flexible molecular descriptors are proposed to develop simple models based solely on constitutional and topological molecular features. A large number of nonconformational descriptors (17974) was used to thoroughly explore the structural characteristics that influence the HER2 inhibitory activity. Three different approaches were explored using: 1) Molecular Descriptors, 2) Flexible Molecular Descriptors, and 3) Hybrid Descriptors. A QSAR model for HER2 inhibitors was successfully developed. Some properties such as electronegativity, aromatic character, and the presence of amino groups appear as molecular characteristics that may have influence in the HER2 inhibitory activity.Facultad de Ciencias ExactasInstituto de Investigaciones Fisicoquímicas Teóricas y Aplicada

QSAR studies of indoyl aryl sulfides and sulfones as reverse transcriptase inhibitors

The inhibitory HIV reverse transcriptase activity of 172 non-nucleoside indoyl aryl sulfones and sulfides is studied with a QSAR analysis, in order to identify the molecular characteristics influencing the interaction with the reverse transcriptase enzyme. This work increases the available QSAR studies of indoyl aryl sulfones and sulfides using the reported experimental EC₅₀ values against HIV-1 wild type (IIIB) in human T-lymphocyte (CEM) cells. Different approaches are proposed, involving 0D, 1D and 2D molecular descriptors from PaDEL freeware, and also based on flexible descriptors from CORAL freeware. Three models are finally presented, which correlate the inhibitory HIV reverse transcriptase activity with good accuracy. It is demonstrated that the established models are predictive in the validation process. The novelty of the present work relies on the development of structure-inhibitory HIV activity relationships, through a computational technique that does not require the knowledge of the molecular conformation during the structural representation. The obtained results would contribute to guide the design of more effective compounds for HIV treatment.Instituto de Investigaciones Fisicoquímicas Teóricas y AplicadasCentro de Investigación y Desarrollo en Ciencias AplicadasCentro de Investigación en Sanidad Vegeta