The synthesis and antibacterial activity of pyrazole-fused tricyclic diterpene derivatives

Li-Gang Yu; Teng-Feng Ni; Wei Gao; Yuan He; Ying-Ying Wang; Hai-Wei Cui; Cai-Guang Yang; Wen-Wei Qiu

doi:10.1016/j.ejmech.2014.11.015

The synthesis and antibacterial activity of pyrazole-fused tricyclic diterpene derivatives

Eur J Med Chem. 2015 Jan 27:90:10-20. doi: 10.1016/j.ejmech.2014.11.015. Epub 2014 Nov 6.

Authors

Li-Gang Yu¹, Teng-Feng Ni², Wei Gao¹, Yuan He³, Ying-Ying Wang¹, Hai-Wei Cui¹, Cai-Guang Yang², Wen-Wei Qiu⁴

Affiliations

¹ Department of Chemistry, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China.
² CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
³ Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
⁴ Department of Chemistry, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China. Electronic address: [email protected].

PMID: 25461307
DOI: 10.1016/j.ejmech.2014.11.015

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.

Keywords: Antibacterial; Cyclization reaction; Diterpene derivative; Multidrug-resistant; Synthesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Crystallography, X-Ray
Diterpenes / chemical synthesis
Diterpenes / chemistry
Diterpenes / pharmacology*
Dose-Response Relationship, Drug
Drug Resistance, Multiple, Bacterial / drug effects*
Fibroblasts / cytology
Humans
Microbial Sensitivity Tests
Models, Molecular
Molecular Structure
Pyrazoles / chemistry
Pyrazoles / pharmacology*
Staphylococcus aureus / drug effects*
Structure-Activity Relationship

Substances

Anti-Bacterial Agents
Diterpenes
Pyrazoles
pyrazole