In Silico Assessment of the Acute Toxicity of Chemicals: Recent Advances and New Model for Multitasking Prediction of Toxic Effect

• Type: Another Publication in an International Scientific Journal
• Date: 2015

Authors

Kleandrova, VV (Author) Other; Luan, F (Author) Other; Speck Planche, A (Author) Other; Natalia N D S Cordeiro (Author) FCUP

Journal

Title: Mini-Reviews in Medicinal Chemistry

Vol. 15

Pages: 677-686

ISSN: 1389-5575

Publisher: Bentham

Indexing

ISI Web of Knowledge - 20 Citations

Scopus - 24 Citations

Other information

Authenticus ID: P-00G-589

DOI: 10.2174/1389557515666150219143604

Abstract (EN): The assessment of acute toxicity is one of the most important stages to ensure the safety of chemicals with potential applications in pharmaceutical sciences, biomedical research, or any other industrial branch. A huge and indiscriminate number of toxicity assays have been carried out on laboratory animals. In this sense, computational approaches involving models based on quantitative-structure activity/toxicity relationships (QSAR/QSTR) can help to rationalize time and financial costs. Here, we discuss the most significant advances in the last 6 years focused on the use of QSAR/QSTR models to predict acute toxicity of drugs/chemicals in laboratory animals, employing large and heterogeneous datasets. The advantages and drawbacks of the different QSAR/QSTR models are analyzed. As a contribution to the field, we introduce the first multitasking (mtk) QSTR model for simultaneous prediction of acute toxicity of compounds by considering different routes of administration, diverse breeds of laboratory animals, and the reliability of the experimental conditions. The mtk-QSTR model was based on artificial neural networks (ANN), allowing the classification of compounds as toxic or non-toxic. This model correctly classified more than 94% of the 1646 cases present in the whole dataset, and its applicability was demonstrated by performing predictions of different chemicals such as drugs, dietary supplements, and molecules which could serve as nanocarriers for drug delivery. The predictions given by the mtk-QSTR model are in very good agreement with the experimental results.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10