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

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.

• Authors: Ana Martins, József Csábi, Attila Balázs, Diána Kitka, Leonard Amaral, József Molnár, András Simon, Gábor Tóth, Attila Hunyadi
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 18 Issue 12 Pg. 15255-75 (Dec 10 2013) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 24335576 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, chemistry, pharmacology)
• Doxorubicin (pharmacology)
• Drug Synergism
• Ecdysteroids (chemical synthesis, chemistry, pharmacology)
• Inhibitory Concentration 50
• Lymphoma (metabolism)
• Mice
• Molecular Structure
• Neoplasms (metabolism)
• Nuclear Magnetic Resonance, Biomolecular
• Structure-Activity Relationship