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

• Published in: Toxicology mechanisms and methods Vol. 30; no. 4; pp. 257 - 265
• Main Authors: Mondal, Dipayan, Ghosh, Kalyan, Baidya, Anurag T. K., Gantait, Anindita Mondal, Gayen, Shovanlal
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 03-05-2020
• Subjects: Animals; Breast cancer; cytotoxicity; Hydrocarbons, Aromatic - chemistry; Hydrocarbons, Aromatic - toxicity; Lethal Dose 50; MCF7; Molecular Structure; Monte Carlo; Monte Carlo Method; Nitro Compounds - chemistry; Nitro Compounds - toxicity; phenylindole; QSAR; Quantitative Structure-Activity Relationship; Rats; Breast cancer; MCF7; Monte Carlo; QSAR; phenylindole; cytotoxicity
• ISSN: 1537-6516; 1537-6524
• DOI: 10.1080/15376516.2019.1709238

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 (LD
50
). 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
1
EC
K
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
0
EC
k
connectivity (R
2
= 0.7386, Q
2
= 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.