Design and Synthesis of Pleuromutilin Derivatives as Antibacterial Agents Using Quantitative Structure–Activity Relationship Model

Zhang, Jiaming; Liu, Qinqin; Zhao, Haoxia; Li, Guiyu; Yi, Yunpeng; Shang, Ruofeng

doi:10.3390/ijms25042256

Open AccessArticle

Design and Synthesis of Pleuromutilin Derivatives as Antibacterial Agents Using Quantitative Structure–Activity Relationship Model

by

Jiaming Zhang

^1,2,

Qinqin Liu

¹,

Haoxia Zhao

¹,

Guiyu Li

¹,

Yunpeng Yi

^2,*

and

Ruofeng Shang

^1,*

¹

Key Laboratory of New Animal Drug Project, Gansu Province/Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture and Rural Affairs/Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China

²

Shandong Provincial Animal and Poultry Green Health Products Creation Engineering Laboratory, Institute of Poultry Science, Shandong Academy of Agricultural Science, Jinan 250023, China

^*

Authors to whom correspondence should be addressed.

Int. J. Mol. Sci. 2024, 25(4), 2256; https://doi.org/10.3390/ijms25042256

Submission received: 12 January 2024 / Revised: 7 February 2024 / Accepted: 8 February 2024 / Published: 13 February 2024

(This article belongs to the Special Issue Rational Design and Synthesis of Bioactive Molecules)

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Abstract

The quantitative structure–activity relationship (QSAR) is one of the most popular methods for the virtual screening of new drug leads and optimization. Herein, we collected a dataset of 955 MIC values of pleuromutilin derivatives to construct a 2D-QSAR model with an accuracy of 80% and a 3D-QSAR model with a non-cross-validated correlation coefficient (r²) of 0.9836 and a cross-validated correlation coefficient (q²) of 0.7986. Based on the obtained QSAR models, we designed and synthesized pleuromutilin compounds 1 and 2 with thiol-functionalized side chains. Compound 1 displayed the highest antimicrobial activity against both Staphylococcus aureus ATCC 29213 (S. aureus) and Methicillin-resistant Staphylococcus aureus (MRSA), with minimum inhibitory concentrations (MICs) < 0.0625 μg/mL. These experimental results confirmed that the 2D and 3D-QSAR models displayed a high accuracy of the prediction function for the discovery of lead compounds from pleuromutilin derivatives.

Keywords: pleuromutilin; QSAR; synthesis; antimicrobial activity; molecular docking

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MDPI and ACS Style

Zhang, J.; Liu, Q.; Zhao, H.; Li, G.; Yi, Y.; Shang, R. Design and Synthesis of Pleuromutilin Derivatives as Antibacterial Agents Using Quantitative Structure–Activity Relationship Model. Int. J. Mol. Sci. 2024, 25, 2256. https://doi.org/10.3390/ijms25042256

AMA Style

Zhang J, Liu Q, Zhao H, Li G, Yi Y, Shang R. Design and Synthesis of Pleuromutilin Derivatives as Antibacterial Agents Using Quantitative Structure–Activity Relationship Model. International Journal of Molecular Sciences. 2024; 25(4):2256. https://doi.org/10.3390/ijms25042256

Chicago/Turabian Style

Zhang, Jiaming, Qinqin Liu, Haoxia Zhao, Guiyu Li, Yunpeng Yi, and Ruofeng Shang. 2024. "Design and Synthesis of Pleuromutilin Derivatives as Antibacterial Agents Using Quantitative Structure–Activity Relationship Model" International Journal of Molecular Sciences 25, no. 4: 2256. https://doi.org/10.3390/ijms25042256

APA Style

Zhang, J., Liu, Q., Zhao, H., Li, G., Yi, Y., & Shang, R. (2024). Design and Synthesis of Pleuromutilin Derivatives as Antibacterial Agents Using Quantitative Structure–Activity Relationship Model. International Journal of Molecular Sciences, 25(4), 2256. https://doi.org/10.3390/ijms25042256

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Design and Synthesis of Pleuromutilin Derivatives as Antibacterial Agents Using Quantitative Structure–Activity Relationship Model

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