Synthesis and structure-activity relationships of novel ecdysteroid dioxolanes as MDR modulators in cancer

Molecules. 2013 Dec 10;18(12):15255-75. doi: 10.3390/molecules181215255.

Abstract

Ecdysteroids, molting hormones of insects, can exert several mild, non-hormonal bioactivities in mammals, including humans. In a previous study, we have found a significant effect of certain derivatives on the ABCB1 transporter mediated multi-drug resistance of a transfected murine leukemia cell line. In this paper, we present a structure-activity relationship study focused on the apolar dioxolane derivatives of 20-hydroxyecdysone. Semi-synthesis and bioactivity of a total of 32 ecdysteroids, including 20 new compounds, is presented, supplemented with their complete 1H- and 13C-NMR signal assignment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / antagonists & inhibitors*
  • Animals
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Combinatorial Chemistry Techniques
  • Dioxolanes / chemical synthesis
  • Dioxolanes / chemistry*
  • Dioxolanes / pharmacology*
  • Doxorubicin / pharmacology
  • Drug Synergism
  • Ecdysteroids / chemical synthesis
  • Ecdysteroids / chemistry*
  • Ecdysteroids / pharmacology*
  • Inhibitory Concentration 50
  • Lymphoma / metabolism
  • Mice
  • Molecular Structure
  • Neoplasms / metabolism*
  • Nuclear Magnetic Resonance, Biomolecular
  • Structure-Activity Relationship

Substances

  • ATP Binding Cassette Transporter, Subfamily B
  • Antineoplastic Agents
  • Dioxolanes
  • Ecdysteroids
  • Doxorubicin
  • formal glycol