Modelling lethality and teratogenicity of zebrafish (Danio rerio) due to β-lactam antibiotics employing the QSTR approach

Nowadays, β-lactam antibiotics are one of the most consumed OTC (over-the-counter) medicines in the world. Its frequent use against several infectious diseases leads to the development of antibiotic resistance. Another unavoidable risk factor of β-lactam antibiotics is environmental toxicity. Numerous terrestrial as well as aquatic species have suffered due to the excessive use of these pharmaceuticals. In this present study, we have performed a toxicity assessment employing a novel in silico technique like quantitative structure–toxicity relationships (QSTRs) to explore toxicity against zebrafish (Danio rerio). We have developed single as well as inter-endpoint QSTR models for the β-lactam compounds to explore important structural attributes responsible for their toxicity, employing median lethal (LC50) and median teratogenic concentration (TC50) as the endpoints. We have shown how an inter-endpoint model can extrapolate unavailable endpoint values with the help of other available endpoint values. To verify the models’ robustness, predictivity, and goodness-of-fit, several universally popular metrics for both internal and external validation were extensively employed in model validation (single endpoint models: r2 = 0.631 − 0.75, Q2F1 = 0.607 − 0.684; inter-endpoint models: r2 = 0.768 − 0.84, Q2F1 = 0.678 − 0.76). Again, these models were engaged in the prediction of these two responses for a true external set of β-lactam molecules without response values to prove the reproducibility of these models.