Predicting the Time-Dependent Toxicities of Binary Mixtures of Five Antibiotics to Sp.- Based on the QSAR Model

Overview

Journal Environ Health (Wash)

Publisher American Chemical Society

Date 2024 Oct 30

PMID 39473888

Authors

Xiachangli Xu

Yongan Liu

Lingyun Mo

Xuehua Li

Junfeng Dai

Litang Qin

Affiliations

Soon will be listed here.

Abstract

Antibiotics may be exposed in a mixed state in natural environments. The toxicity of antibiotic mixtures exhibits time-dependent characteristics, and data on the time-dependent toxicity of antibiotic mixtures is also relatively lacking. In this study, the toxicities of 45 binary mixtures composed of five antibiotics were investigated against sp.- () at multiple exposure times (4, 6, 8, 10, and 12 h). Quantitative structure-activity relationship (QSAR) models were developed for predicting the time-dependent toxicities of 45 binary mixtures. The results showed that the best QSAR models presented coefficient of determination ( ) of (0.818-0.913) and explained variance in prediction leave-one-out ( ) of (0.781-0.894) and predictive ability ( , , > 0.682, concordance correlation coefficient > 0.859). The values of QSAR models outperformed the (0.628-0.810) of the conventional concentration addition models and the (0.654-0.792) of the independent action models. Furthermore, the QSAR models showed higher and values at 4 h compared to other exposure times. Specifically, the model at the 30% effective concentration (EC) had of 0.902 and of 0.883, while the model at the 50% effective concentration (EC) had of 0.913 and of 0.894. The CATS2D_04_DP descriptor was found to be the most dominant and negatively correlated factor influencing the toxicity of mixed antibiotics against in the nine QSAR models developed over five exposure times. The reduction in the number of DP pharmacophore point pairs with a topological distance of 4 in the represented molecules is the primary cause for the rise in the time-dependent toxicity of the antibiotics against .

Citing Articles

Effect of Fluorine Atoms and Piperazine Rings on Biotoxicity of Norfloxacin Analogues: Combined Experimental and Theoretical Study.

Yang C, Wang X, Zhao X, Wu Y, Lin J, Zhao Y Environ Health (Wash). 2024; 2(12):886-901.

PMID: 39722844 PMC: 11667292. DOI: 10.1021/envhealth.4c00095.

References

Yang J, Ahmed W, Mehmood S, Ou W, Li J, Xu W . Evaluating the Combined Effects of Erythromycin and Levofloxacin on the Growth of sp. and Understanding the Underlying Mechanisms. Plants (Basel). 2023; 12(13). PMC: 10347161. DOI: 10.3390/plants12132547. View

Zhou L, Ying G, Liu S, Zhao J, Yang B, Chen Z . Occurrence and fate of eleven classes of antibiotics in two typical wastewater treatment plants in South China. Sci Total Environ. 2013; 452-453:365-76. DOI: 10.1016/j.scitotenv.2013.03.010. View

Wang H, Wang N, Wang B, Fang H, Fu C, Tang C . Antibiotics detected in urines and adipogenesis in school children. Environ Int. 2016; 89-90:204-11. DOI: 10.1016/j.envint.2016.02.005. View

Xu W, Zhang G, Li X, Zou S, Li P, Hu Z . Occurrence and elimination of antibiotics at four sewage treatment plants in the Pearl River Delta (PRD), South China. Water Res. 2007; 41(19):4526-34. DOI: 10.1016/j.watres.2007.06.023. View

Wang D, Ning Q, Dong J, Brooks B, You J . Predicting mixture toxicity and antibiotic resistance of fluoroquinolones and their photodegradation products in Escherichia coli. Environ Pollut. 2020; 262:114275. DOI: 10.1016/j.envpol.2020.114275. View

Zou X, Zhou X, Lin Z, Deng Z, Yin D . A docking-based receptor library of antibiotics and its novel application in predicting chronic mixture toxicity for environmental risk assessment. Environ Monit Assess. 2012; 185(6):4513-27. DOI: 10.1007/s10661-012-2885-5. View

Kaneko H . Examining variable selection methods for the predictive performance of regression models and the proportion of selected variables and selected random variables. Heliyon. 2021; 7(6):e07356. PMC: 8237311. DOI: 10.1016/j.heliyon.2021.e07356. View

Gramatica P, Cassani S, Chirico N . QSARINS-chem: Insubria datasets and new QSAR/QSPR models for environmental pollutants in QSARINS. J Comput Chem. 2014; 35(13):1036-44. DOI: 10.1002/jcc.23576. View

Rybak M . The pharmacokinetic and pharmacodynamic properties of vancomycin. Clin Infect Dis. 2005; 42 Suppl 1:S35-9. DOI: 10.1086/491712. View

10.

Schuurmann G, Ebert R, Chen J, Wang B, Kuhne R . External validation and prediction employing the predictive squared correlation coefficient test set activity mean vs training set activity mean. J Chem Inf Model. 2008; 48(11):2140-5. DOI: 10.1021/ci800253u. View

11.

Zhang F, Wang Z, Peijnenburg W, Vijver M . Machine learning-driven QSAR models for predicting the mixture toxicity of nanoparticles. Environ Int. 2023; 177:108025. DOI: 10.1016/j.envint.2023.108025. View

12.

Evans R, Martin O, Faust M, Kortenkamp A . Should the scope of human mixture risk assessment span legislative/regulatory silos for chemicals?. Sci Total Environ. 2015; 543(Pt A):757-764. DOI: 10.1016/j.scitotenv.2015.10.162. View

13.

Wang D, Wu X, Lin Z, Ding Y . A comparative study on the binary and ternary mixture toxicity of antibiotics towards three bacteria based on QSAR investigation. Environ Res. 2018; 162:127-134. DOI: 10.1016/j.envres.2017.12.015. View

14.

Chirico N, Gramatica P . Real external predictivity of QSAR models. Part 2. New intercomparable thresholds for different validation criteria and the need for scatter plot inspection. J Chem Inf Model. 2012; 52(8):2044-58. DOI: 10.1021/ci300084j. View

15.

Dou R, Liu S, Mo L, Liu H, Deng F . A novel direct equipartition ray design (EquRay) procedure for toxicity interaction between ionic liquid and dichlorvos. Environ Sci Pollut Res Int. 2010; 18(5):734-42. DOI: 10.1007/s11356-010-0419-7. View

16.

Santas-Miguel V, Rodriguez-Gonzalez L, Nunez-Delgado A, Diaz-Ravina M, Arias-Estevez M, Fernandez-Calvino D . The Toxicity Exerted by the Antibiotic Sulfadiazine on the Growth of Soil Bacterial Communities May Increase over Time. Int J Environ Res Public Health. 2020; 17(23). PMC: 7729481. DOI: 10.3390/ijerph17238773. View

17.

Li R, Lee S, Kong C . Correlation between bactericidal activity and postantibiotic effect for five antibiotics with different mechanisms of action. J Antimicrob Chemother. 1997; 40(1):39-45. DOI: 10.1093/jac/40.1.39. View

18.

Dudley M . Combination beta-lactam and beta-lactamase-inhibitor therapy: pharmacokinetic and pharmacodynamic considerations. Am J Health Syst Pharm. 1995; 52(6 Suppl 2):S23-8. DOI: 10.1093/ajhp/52.6_Suppl_2.S23. View

19.

Salvito D, Senna R, Federle T . A framework for prioritizing fragrance materials for aquatic risk assessment. Environ Toxicol Chem. 2002; 21(6):1301-8. View

20.

Myint K, Xie X . Recent advances in fragment-based QSAR and multi-dimensional QSAR methods. Int J Mol Sci. 2010; 11(10):3846-66. PMC: 2996787. DOI: 10.3390/ijms11103846. View