Synthesis of drimanyl indole fragments of drimentine alkaloids and their antibacterial activities

Bioorg Med Chem Lett. 2025 Feb 1:116:130040. doi: 10.1016/j.bmcl.2024.130040. Epub 2024 Nov 24.

Abstract

Two types of drimanyl indole fragments of drimentine alkaloids were synthesized and evaluated their in vitro antibacterial activities using minimum inhibitory concentration. Analysis of structure-activity relationship against Ralstonia solanacearum revealed that fragment I exhibited superior inhibitory activity compared to fragment II. Notably, free NH of the indole motif was essential for antibacterial activity, while C12OH of the drimane skeleton was beneficial for enhancing the inhibitory effect. Compound 2, possessing these structural features, showed the highest activity to R. solanacearum among all the tested compounds with a MIC value of 8 µg/mL, indicating its potential as a promising lead for the development of novel antibiotics.

Keywords: Antibacterial activity; Drimentine; Fischer indolization; Sclareol; Structure–activity relationship.

MeSH terms

  • Alkaloids / chemical synthesis
  • Alkaloids / chemistry
  • Alkaloids / pharmacology
  • Anti-Bacterial Agents* / chemical synthesis
  • Anti-Bacterial Agents* / chemistry
  • Anti-Bacterial Agents* / pharmacology
  • Dose-Response Relationship, Drug
  • Indoles* / chemical synthesis
  • Indoles* / chemistry
  • Indoles* / pharmacology
  • Microbial Sensitivity Tests*
  • Molecular Structure
  • Ralstonia solanacearum* / drug effects
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Indoles
  • Alkaloids