Advances in chemistry and bioactivity of parthenolide

Nat Prod Rep. 2020 Apr 1;37(4):541-565. doi: 10.1039/c9np00049f. Epub 2019 Nov 25.

Abstract

Review covering up to 07/2019(-)-Parthenolide is a germacrane sesquiterpene lactone, available in ample amounts from the traditional medical plant feverfew (Tanacetum parthenium). Acting as a covalently reactive compound, it displays anti-inflammatory, redox-modulating, and epigenetic activities, as well as selective cytotoxicity towards cancer stem and progenitor cells. Furthermore, parthenolide was found to modulate microtubule dynamics by interfering with the detyrosination of α-tubulin, a specific posttranslational modification of the cytoskeleton. This review interfaces recently achieved parthenolide syntheses with strategies for bioactivity-based derivatization. Furthermore, chemical probe development from parthenolide is discussed, leading to a qualified summary of reported biological activities and implicated or identified targets. Special emphasis is given to parthenolide-induced microtubule modulation and the recently characterized tubulin carboxypeptidase enzymes involved in nerve (re)growth, cardiac muscle cell function, and metastasis development.

Publication types

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

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Carboxypeptidases / antagonists & inhibitors
  • Cyclization
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Molecular Structure
  • Sesquiterpenes / chemical synthesis
  • Sesquiterpenes / chemistry*
  • Sesquiterpenes / metabolism
  • Sesquiterpenes / pharmacology*
  • Sesquiterpenes, Germacrane / chemistry
  • Stereoisomerism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antineoplastic Agents, Phytogenic
  • Sesquiterpenes
  • Sesquiterpenes, Germacrane
  • parthenolide
  • Carboxypeptidases
  • tyrosyltubulin carboxypeptidase