Novel pleuromutilin derivatives with substituted 6-methylpyrimidine: Design, synthesis and antibacterial evaluation

Robust and predictive 2D/3D-QSAR models for predicting the activities of novel pleuromutilin derivatives as antibacterial agents

“…In this work, the novel pleuromutilin derivatives were chosen from Ref. [20]. The Initially, the antibacterial activities MIC (μM) are converted to the corresponding pMIC (-logMIC) values, and employed as dependent variable in the QSAR analyses.…”

“…Recently, some groups have been endeavoring to synthesize novel pleuromutilin derivatives with improved activities [20][21][22]. However, it is time-consuming and material redundant for the synthesis of range of new derivatives.…”

“…Conversely, energy will be saved when the information is derived between the structure and the activities, which is valuable for design novel compounds prior to in vivo experiment. So in the present work, using multiple linear regression (MLR) method for two dimensional quantitative structure-activity relationship (2D-QSAR), comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) approaches for 3D-QSAR were carried out upon a series of novel synthesized pleuromutilin derivatives with substituted 6-methylpyrimidine moieties [20]. The analysis would provide a useful platform for the prediction of novel pleuromutilin derivatives activities and aid the design of new chemical entities with potential antibacterial activities.…”

Synthesis and in vitro evaluation of antibacterial and antibiofilm activities of novel triphenylphosphonium‐functionalized substituted pyrimidines

“…Among heterocyclic compounds, pyrimidine derivatives are an important class of compounds with various biological properties, including antibacterial activity against Gram‐positive and Gram‐negative bacteria (Basha & Goudgaon, 2021; Nadar & Khan, 2022). The presence of amino(alkyl) residues in the thiopyrimidine scaffold is useful for obtaining good antimicrobial activity of the compounds (Attia et al., 2014; Fan et al., 2020). Furthermore, thiophenyl‐substituted pyrimidine derivative (F20) shows significant antibacterial activity against Gram‐positive bacteria, which include drug‐resistant bacteria like methicillin‐resistant Staphylococcus aureus (MRSA) and vancomycin‐resistant Enterococcus (VRE) (Fang et al., 2019).…”

A click chemistry approach to pleuromutilin derivatives, evaluation of anti-MRSA activity and elucidation of binding mode by surface plasmon resonance and molecular docking

“…Previous studies on the structure-activity relationship (SAR) have shown that the C-14 side chain of pleuromutilin derivatives containing thioether bonds, basic groups, or heterocyclic rings containing polar groups can improve their antibacterial activity 17–23 . In our previous work, some novel pleuromutilin analogues which having a piperazine as linker displayed potent in vitro and in vivo antibacterial activity against S. aureus (ATCC 29213) 20 , 21 .…”