title: The synthesis and antibacterial activity of pyrazole-fused tricyclic diterpene derivatives.
abstract: The diterpenoid compound 5 was identified as an antibacterial lead in our screening of small synthetic natural product-like (NPL) library. A series of novel diterpene derivatives were synthesized and investigated for their activity against Staphylococcus aureus Newman strain and multidrug-resistant strains (NRS-1, NRS-70, NRS-100, NRS-108 and NRS-271). Among the compounds tested, 42 and 43 showed highest activity with a MIC of 1 μg/mL against strain Newman, 45 and 52 showed the most potent activity with MIC values of 0.71-3.12 μg/mL against five multidrug-resistant S. aureus. All high-antimicrobial active compounds showed no obvious toxicity to human fibroblast (HAF) cells at the MIC concentration.
authors.affiliation: Department of Chemistry, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China.
authors.forename: Li-Gang
authors.initials: LG
authors.lastname: Yu
authors.affiliation: CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Teng-Feng
authors.initials: TF
authors.lastname: Ni
authors.affiliation: Department of Chemistry, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Chemistry, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Wang
authors.affiliation: Department of Chemistry, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China.
authors.forename: Hai-Wei
authors.initials: HW
authors.lastname: Cui
authors.affiliation: CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Cai-Guang
authors.initials: CG
authors.lastname: Yang
authors.affiliation: Department of Chemistry, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China. Electronic address: wwqiu@chem.ecnu.edu.cn.
authors.forename: Wen-Wei
authors.initials: WW
authors.lastname: Qiu
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004224:Diterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D004224:Diterpenes; D011720:Pyrazoles; C031280:pyrazole
keywords: Antibacterial; Cyclization reaction; Diterpene derivative; Multidrug-resistant; Synthesis