In silico modelling of acute toxicity of 1, 2, 4-triazole antifungal agents towards zebrafish (Danio rerio) embryos: Application of the Small Dataset Modeller tool.

Abstract

Nowadays there is a widespread use of triazole antifungal agents to kill broad classes of fungi in farming lands and to protect herbs, fruits and grains. These agents further deposit into the aquatic systems causing toxicity to the living aquatic creatures, which can then affect human beings. Considering this issue, risk assessment of these toxic chemicals is a very essential task. Due to the inadequate experimental data on acute toxicity of antifungal agents containing the 1, 2, 4-triazole ring, higher testing costs along with the regulatory restrictions and the international regulations to lessen animal testing emphasize on in silico techniques such as quantitative structure-activity relationship (QSAR) studies. The application of QSAR modelling has created an easier avenue to predict activity/property/toxicity of newly synthesized compounds. In the present study, we have used 23 antifungal agents containing the 1, 2, 4-triazole ring to develop 2D-QSAR models and explore their structural attributes crucial for acute toxicity towards embryonic phase of zebrafish (Danio rerio). Here, we have employed simple 2D descriptors to develop the QSAR models. The models were evolved by executing the Small Dataset Modeller tool (https://dtclab.webs.com/software-tools), and the validation of the models was achieved employing different precise validation principles. The statistical validation metrics confirm that built models are robust, useful and well predictive to forecast the acute toxicity of new compounds.