Identification of structural fingerprints for in vivo toxicity by using Monte Carlo based QSTR modeling of nitroaromatics.

Abstract:

:Monte Carlo based method by using either SMILES based or combination of SMILES and Graph-based descriptors is an important strategy to build the QSAR/QSTR model for prediction of different biological endpoints. In this study, Monte Carlo based QSTR approach was applied to the dataset of 90 nitroaromatic compounds related to their in vivo toxicity, represented by 50% lethal dose concentration for rats (LD50). Both classification and regression-based QSTR models were developed to get an idea about different fingerprints for promoters and hinderers of nitroaromatics toxicity. The best classification model was obtained by using SMILES and graph-based (GAO) descriptor with 1ECK connectivity (sensitivity = 0.7143, specificity = 1.0000, accuracy = 0.8889, and MCC = 0.7774). The best regression model calculated by using SMILES and hydrogen-suppressed graph descriptors with 0ECk connectivity (R2 = 0.7386, Q2 = 0.6315, S   =   0.467, and MAE = 0.340). Finally, a consensus QSTR model was generated to predict efficiently the toxicity of new compounds. The study highlighted that the comparative QSTR models by using the Monte Carlo method can also be generated and will be a useful tool for structural fingerprint analysis in case of nitroaromatics for preliminary evaluation of its toxicity to mammals.

journal_name

Toxicol Mech Methods

authors

Mondal D,Ghosh K,Baidya ATK,Gantait AM,Gayen S

doi

10.1080/15376516.2019.1709238

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

257-265

issue

4

eissn

1537-6516

issn

1537-6524

journal_volume

30

pub_type

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