title: Design, synthesis, and antibacterial activity of novel pleuromutilin derivatives bearing an amino thiazolyl ring.
abstract: A series of novel pleuromutilin derivatives containing the amino thiazolyl ring were designed, synthesized, and evaluated for their antibacterial activities in vitro against Gram-positive clinical bacteria. All the target compounds showed better aqueous solubility compared with the lead compound (10). Most compounds displayed strong antibacterial activities against both susceptible and resistant bacteria, particularly for the compound (12f) which showed extraordinary antibacterial properties superior to amoxicillin and tiamulin. Molecular docking studies revealed that the amino thiazolyl ring, the side chains of the pleuromutilin derivatives, can be adopted in the binding pocket of the 50S ribosomal subunit near the mutilin core. Therefore, our novel findings may provide new insights into the design of novel pleuromutilin derivatives and lay the basis for further studies on these promising antibiotics for human clinical use.
authors.affiliation: Department of Pharmacy, School of Medical, Nantong University, Nantong, P. R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Ling
authors.forename: Xinyang
authors.initials: X
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Jianghe
authors.initials: J
authors.lastname: Yu
authors.forename: Junming
authors.initials: J
authors.lastname: Tang
authors.forename: Donggeng
authors.initials: D
authors.lastname: Wang
authors.forename: Guangtong
authors.initials: G
authors.lastname: Chen
authors.forename: Jinhua
authors.initials: J
authors.lastname: Huang
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Li
authors.forename: Heng
authors.initials: H
authors.lastname: Zheng
mesh_terms: D000658:Amoxicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004224:Diterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests / Q000379:methods / Q000706:statistics & numerical data; D062105:Molecular Docking Simulation / Q000379:methods; D011083:Polycyclic Compounds; D012995:Solubility; D013329:Structure-Activity Relationship; D000097567:Pleuromutilins
chemical_list: D000658:Amoxicillin; D000900:Anti-Bacterial Agents; D004224:Diterpenes; D011083:Polycyclic Compounds; D000097567:Pleuromutilins; C014224:tiamulin