Design and Synthesis of Pleuromutilin Derivatives as Antibacterial Agents Using Quantitative Structure–Activity Relationship Model.
- Resource Type
- Article
- Authors
- Zhang, Jiaming; Liu, Qinqin; Zhao, Haoxia; Li, Guiyu; Yi, Yunpeng; Shang, Ruofeng
- Source
- International Journal of Molecular Sciences. Feb2024, Vol. 25 Issue 4, p2256. 13p.
- Subject
- *STRUCTURE-activity relationships
*ANTIBACTERIAL agents
*METHICILLIN-resistant staphylococcus aureus
*QSAR models
*STAPHYLOCOCCUS aureus
- Language
- ISSN
- 1661-6596
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. [ABSTRACT FROM AUTHOR]