Lathyrane diterpenoids with multidrug resistance reversal activity from the tubers of Euphorbia antiquorum

Phytochemistry. 2024 Dec:228:114233. doi: 10.1016/j.phytochem.2024.114233. Epub 2024 Aug 5.

Abstract

Nine previously unreported lathyrane diterpenoids named euphorantesters A-I, along with 16 known analogues, have been separated from the tubers of Euphorbia antiquorum. Their structures were established by means of spectroscopic analyses, time-dependent density functional theory based electronic circular dichroism calculation and single crystal X-ray crystallography. Their reversal ability against P-glycoprotein-mediated multidrug resistance (MDR) in MCF-7/ADR cell line was then evaluated, and 15 ones exhibited moderate MDR reversal activity with reversal fold falling in the range of 1.12-13.15. The most active euphorantester B could effectively increase the sensitivity of MCF-7/ADR cell to adriamycin comparably to the reference drug verapamil.

Keywords: Euphorantester; Euphorbia antiquorum; Euphorbiaceae; Lathyrane diterpenoid; Multidrug resistance.

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Cell Proliferation / drug effects
  • Crystallography, X-Ray
  • Diterpenes* / chemistry
  • Diterpenes* / isolation & purification
  • Diterpenes* / pharmacology
  • Dose-Response Relationship, Drug
  • Doxorubicin / pharmacology
  • Drug Resistance, Multiple* / drug effects
  • Drug Resistance, Neoplasm* / drug effects
  • Drug Screening Assays, Antitumor
  • Euphorbia* / chemistry
  • Humans
  • MCF-7 Cells
  • Models, Molecular
  • Molecular Conformation
  • Molecular Structure
  • Plant Tubers* / chemistry
  • Structure-Activity Relationship

Substances

  • Diterpenes
  • lathyrane
  • Antineoplastic Agents, Phytogenic
  • Doxorubicin