Synthesis and Cytotoxic Activity of Azine Derivatives of 6-Hydroxyxanthanodiene

Curr Cancer Drug Targets. 2020;20(9):666-674. doi: 10.2174/1568009620999200421200338.

Abstract

Background: The conjugates of the sesquiterpene lactone of the eremophilane series of 6- hydroxyxanthanodiene with hydrogenated azines (piperidines and piperazines) have been synthesized and identified by NMR spectrometer.

Objective: A lactone with an unusual skeleton "6-hydroxyxanthanodiene" was extracted from the plant Elecampane (Inula helenium L) and identified various species with NMR spectrometer.

Methods: The cytotoxic, mitochondrial, and antioxidant activities on different tumor lines such as A549, HCT116, RD and Jurkat were investigated and determined possible mechanisms.

Results: The results showed that the most potent compound was IIIi exhibiting highest cytotoxicity against RD cells (IC50 25.23 ± 0.04 μM), depolarized the mitochondrial membrane and was an effective antioxidant (IC50 inhibition of LP 10.68 ± 3.21 μM) without any toxic side effect on healthy cells.

Conclusion: The conjugates of sesquiterpene lactone 6-hydroxyxanthanodiene III and hydrogenated azines may help to design potential promising anticancer drugs.

Keywords: 6-hydroxyxanthanodiene; anticancer drug; antioxidants; apoptosis; azines; cytotoxicity; mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Cell Survival / drug effects
  • HCT116 Cells
  • Humans
  • Inhibitory Concentration 50
  • Inula / chemistry*
  • Jurkat Cells
  • Lactones / chemistry
  • Lactones / pharmacology*
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Rats
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / pharmacology*

Substances

  • Antineoplastic Agents, Phytogenic
  • Antioxidants
  • Lactones
  • Plant Extracts
  • Sesquiterpenes