Synthesis, biological activities and docking studies of pleuromutilin derivatives with piperazinyl urea linkage
| Autor: | Feng Shang, Chuan Xie, Xinghui Yao, Liu Yang, Rushiya Shao, Dongfang Liu, Zhouyu Wang, Yuanyuan Zhang, Jing Yu, Chunxia Wu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Methicillin-Resistant Staphylococcus aureus
piperazinyl urea synthesis medicine.drug_class Antibiotics Pleuromutilin RM1-950 Microbial Sensitivity Tests MRSA 01 natural sciences chemistry.chemical_compound Docking (dog) Antibiotic resistance Drug Discovery medicine Humans Urea Polycyclic Compounds Pharmacology Linkage (software) Molecular Structure 010405 organic chemistry High mortality biological activities General Medicine 0104 chemical sciences Anti-Bacterial Agents Molecular Docking Simulation 010404 medicinal & biomolecular chemistry HEK293 Cells Biochemistry chemistry Therapeutics. Pharmacology Diterpenes Research Article Research Paper |
| Zdroj: | Journal of Enzyme Inhibition and Medicinal Chemistry article-version (VoR) Version of Record Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 36, Iss 1, Pp 764-775 (2021) |
| ISSN: | 1475-6374 |
| Popis: | Antibiotics resistance is becoming increasingly common, involving almost all antibiotics on the market. Diseases caused by drug resistant bacteria, such as MRSA, have high mortality and negatively affect public health. The development of new drugs would be an effective means of solving this problem. Modifications based on bioactive natural products could greatly shorten drug development time and improve success rate. Pleuromutilin, a natural product from the basidiomycete bacterial species, is a promising antibiotic candidate. In this study, a series of novel pleuromutilin derivatives possessing piperazinyl urea linkage were efficiently synthesised, and their antibacterial activities and bactericidal properties were evaluated via MIC, MBC and Time-kill kinetics assays. The results showed that all compounds exhibited potent activities against tested strains, especially MRSA strains with MIC values as low as 0.125 μg/mL; 8 times lower than that of marketed antibiotic Tiamulin. Docking studies indicate substituted piperazinyl urea derivatives could provide hydrogen bonds and initiate π-π stacking between molecules and surrounding residues. |
| Databáze: | OpenAIRE |
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