Jatrophane diterpenoids with multidrug-resistance modulating activity from the latex of Euphorbia nicaeensis

Gordana Krstić; Milka Jadranin; Nina M Todorović; Milica Pešić; Tijana Stanković; Ivana S Aljančić; Vele V Tešević

doi:10.1016/j.phytochem.2018.01.016

Jatrophane diterpenoids with multidrug-resistance modulating activity from the latex of Euphorbia nicaeensis

Phytochemistry. 2018 Apr:148:104-112. doi: 10.1016/j.phytochem.2018.01.016. Epub 2018 Feb 6.

Authors

Gordana Krstić¹, Milka Jadranin², Nina M Todorović², Milica Pešić³, Tijana Stanković³, Ivana S Aljančić⁴, Vele V Tešević¹

Affiliations

¹ Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, 11158, Belgrade, Serbia.
² Institute of Chemistry, Technology and Metallurgy, Center for Chemistry, University of Belgrade, Njegoševa 12, 11000, Belgrade, Serbia.
³ Institute for Biological Research, Department of Neurobiology, University of Belgrade, Bulevar Despota Stefana 142, 11060, Belgrade, Serbia.
⁴ Institute of Chemistry, Technology and Metallurgy, Center for Chemistry, University of Belgrade, Njegoševa 12, 11000, Belgrade, Serbia. Electronic address: aljancic@chem.bg.ac.rs.

PMID: 29421506
DOI: 10.1016/j.phytochem.2018.01.016

Abstract

Seven previously undescribed jatrophane diterpenoids, nicaeenin A-G, with eight known jatrophane diterpenoids, namely euphodendrophanes A-C, F, N, O, Q, S, were isolated from latex of Euphorbia nicaeensis collected in Serbia. The chemical structures of the compounds were determined by spectroscopic analysis including 1D and 2D NMR and HRESIMS experiments. All but one of the previously undescribed jatrophanes, showed significant potential to inhibit P-glycoprotein (P-gp) activity in two MDR cancer cells (NCI-H460/R and DLD1-TxR). The most powerful were nicaeenin F and nicaeenin G. Moreover nicaeenin G significantly stronger sensitized NCI-H460/R cells to DOX than Dex-VER.

Keywords: Diterpenoids; Euphorbia nicaeensis; Euphorbiaceae; Isolation; Jatrophanes; Multi-drug resistance; P-glycoprotein; Structutre determination.

MeSH terms

ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors
Antineoplastic Agents, Phytogenic / chemistry
Diterpenes / chemistry
Diterpenes / isolation & purification*
Diterpenes / pharmacology*
Drug Resistance, Multiple / drug effects
Drug Resistance, Neoplasm / drug effects
Euphorbia / chemistry*
Humans
Latex / pharmacology*
Molecular Structure
Nuclear Magnetic Resonance, Biomolecular
Serbia
Structure-Activity Relationship

Substances

ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily B, Member 1
Antineoplastic Agents, Phytogenic
Diterpenes
Latex
jatrophane