Synthesis and evaluation of novel pleuromutilin derivatives targeting the 50S ribosomal subunit for antibacterial ability

Liu, Qinqin; Zhang, Hongjuan; Yi, YunPeng; Wang, Panpan; Pu, Wanxia; Wang, Shengyi; Shang, Ruofeng

doi:10.1016/j.ejmech.2023.115882

Cited by 2 publications

(1 citation statement)

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“…The results showed that the affinity free energy of compound 1 and 2 was −9.69 and −8.13 kcal/mol, respectively. The hydrogen bonds formed between the hydroxyl groups (eight-membered ring) and C=O (ester) of the docked compounds and the residues of G-2532 and G-2088 were the key interactions (Figure 5B,C), which is similar to our previous report [28]. However, the carbonyl in the side chain of compound 1 formed an additional hydrogen bond with A-2466 (Figure 5B) when compared to compound 2.…”

Section: Molecular Docking Studysupporting

confidence: 86%

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

Zhang,

Liu,

Zhao

et al. 2024

IJMS

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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.

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Section: Molecular Docking Studysupporting

confidence: 86%