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

IF 2.3 3区 环境科学与生态学 Q3 CHEMISTRY, MULTIDISCIPLINARY
A Nath, P K Ojha, K Roy
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引用次数: 0

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, 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.

利用 QSTR 方法模拟β-内酰胺类抗生素对斑马鱼(Danio rerio)的致死率和致畸性。
如今,β-内酰胺类抗生素是世界上消费量最大的 OTC(非处方药)之一。频繁使用β-内酰胺类抗生素治疗多种传染病导致了抗生素耐药性的产生。β-内酰胺类抗生素的另一个不可避免的风险因素是环境毒性。大量陆生和水生物种因过度使用这些药物而受害。在本研究中,我们采用了一种新型的硅学技术,如定量结构-毒性关系(QSTRs),对斑马鱼(Danio rerio)的毒性进行了评估。我们采用中位致死浓度(LC50)和中位致畸浓度(TC50)作为端点,为 β-内酰胺化合物开发了单端点和端点间 QSTR 模型,以探索导致其毒性的重要结构属性。我们展示了端点间模型如何借助其他可用端点值来推断不可用的端点值。为了验证模型的稳健性、预测性和拟合优度,我们在模型验证中广泛采用了几种普遍流行的内部和外部验证指标(单端点模型:r2 = 0.631 - 0.75,Q2F1 = 0.607 - 0.684;端点间模型:r2 = 0.768 - 0.84,Q2F1 = 0.678 - 0.76)。为了证明这些模型的可重复性,我们再次使用这些模型对没有反应值的β-内酰胺分子的真实外部集进行了这两种反应的预测。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
5.20
自引率
20.00%
发文量
78
审稿时长
>24 weeks
期刊介绍: SAR and QSAR in Environmental Research is an international journal welcoming papers on the fundamental and practical aspects of the structure-activity and structure-property relationships in the fields of environmental science, agrochemistry, toxicology, pharmacology and applied chemistry. A unique aspect of the journal is the focus on emerging techniques for the building of SAR and QSAR models in these widely varying fields. The scope of the journal includes, but is not limited to, the topics of topological and physicochemical descriptors, mathematical, statistical and graphical methods for data analysis, computer methods and programs, original applications and comparative studies. In addition to primary scientific papers, the journal contains reviews of books and software and news of conferences. Special issues on topics of current and widespread interest to the SAR and QSAR community will be published from time to time.
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