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

ABSTRACT

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, Q²_F1 = 0.607 − 0.684; inter-endpoint models: r² = 0.768 − 0.84, Q²_F1 = 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.

KEYWORDS:

• QSTR
• LC₅₀
• TC₅₀
• β-lactam antibiotics
• inter-endpoint modelling

Acknowledgements

AN expresses gratitude to the Jadavpur University administration for providing the required research facilities.

Disclosure statement

No potential conflict of interest was reported by the authors.

Supplementary material

Supplemental data for this article can be accessed at: https://doi.org/10.1080/1062936X.2024.2378797.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.