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

• The diterpenoid compound 5 was identified as an antibacterial lead.
• A series of diterpene derivatives were designed and synthesized based on the lead.
• The antibacterial activities were investigated against several Staphylococcus aureus strains.
• Compounds 45 and 52 showed the most potent antibacterial activity.

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.

A series of novel natural product-like (NPL) 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).Figure optionsDownload as PowerPoint slide