title: [Synthesis and biological evaluation of novel pleuromutilin derivatives with nitrogen-containing heterocycles as antibacterial agents].
abstract: A series of new pleuromutilins derivatives were designed and synthesized through coupling 2-aminothiazole ring of WL001 with different nitrogen-containing substituted heterocycles in the side chain. Their biological activities were evaluated against both Gram-positive and Gram-negative clinical bacteria in vitro Most new compounds displayed specificity to certain strain of bacteria. Particularly, compounds with saturated nitrogen-containing heterocycles exhibited significant antibacterial activities (0.062 5-8 µg · mL(-1)) superior or similar to those of amoxicillin, tiamulin and levofloxcin. Furthermore, treatment with 15a and 15b having piperidine or morpholine residues also could effectively inhibit Gram-negative bacteria. Therefore, our novel findings may provide a new insight into the design of novel pleuromutilin derivatives and lay the basis for further studies on the treatment of drug-resistance of pathogenic bacteria.
authors.forename: Xin-yang
authors.initials: XY
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.forename: Duo
authors.initials: D
authors.lastname: Wang
authors.forename: Xiang-dong
authors.initials: XD
authors.lastname: Chen
authors.forename: Yong
authors.initials: Y
authors.lastname: Ling
authors.forename: Xiao-li
authors.initials: XL
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
mesh_terms: D000658:Amoxicillin; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry*; D004224:Diterpenes / Q000138:chemical synthesis / Q000737:chemistry; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D009584:Nitrogen; D011083:Polycyclic Compounds; D013329:Structure-Activity Relationship; D000097567:Pleuromutilins
chemical_list: D000658:Amoxicillin; D000900:Anti-Bacterial Agents; D004224:Diterpenes; D064704:Levofloxacin; D009584:Nitrogen; D011083:Polycyclic Compounds; D000097567:Pleuromutilins; C014224:tiamulin