Ingol, ent-atisane, and stachane-type diterpenoids from Euphorbia deightonii with multidrug resistance reversing activity

Muhammad Bello Saidu; Norbert Kúsz; Róbert Berkecz; Bálint Rácz; Gabriella Spengler; Judit Hohmann; Dóra Rédei

doi:10.1016/j.phytochem.2022.113344

Ingol, ent-atisane, and stachane-type diterpenoids from Euphorbia deightonii with multidrug resistance reversing activity

Phytochemistry. 2022 Dec:204:113344. doi: 10.1016/j.phytochem.2022.113344. Epub 2022 Aug 8.

Authors

Muhammad Bello Saidu¹, Norbert Kúsz², Róbert Berkecz³, Bálint Rácz⁴, Gabriella Spengler⁵, Judit Hohmann⁶, Dóra Rédei⁷

Affiliations

¹ Department of Pharmacognosy, University of Szeged, 6720, Szeged, Eötvös u. 6., Hungary. Electronic address: bello.saidu@pharmacognosy.hu.
² Department of Pharmacognosy, University of Szeged, 6720, Szeged, Eötvös u. 6., Hungary. Electronic address: kusznorbert@gmail.com.
³ Institute of Pharmaceutical Analysis, University of Szeged, 6720, Szeged, Somogyi u. 4., Hungary. Electronic address: berkecz.robert@szte.hu.
⁴ Department of Medical Microbiology, Albert Szent-Györgyi Medical School, University of Szeged, 6725, Szeged, Dóm Tér 10., Hungary. Electronic address: racz.balint@med.u-szeged.hu.
⁵ Department of Medical Microbiology, Albert Szent-Györgyi Medical School, University of Szeged, 6725, Szeged, Dóm Tér 10., Hungary. Electronic address: spengler.gabriella@med.u-szeged.hu.
⁶ Department of Pharmacognosy, University of Szeged, 6720, Szeged, Eötvös u. 6., Hungary; Interdisciplinary Centre of Natural Products, University of Szeged, 6720, Szeged, Eötvös u. 6., Hungary. Electronic address: hohmann.judit@szte.hu.
⁷ Department of Pharmacognosy, University of Szeged, 6720, Szeged, Eötvös u. 6., Hungary. Electronic address: redei.dora.judit@szte.hu.

PMID: 35952771
DOI: 10.1016/j.phytochem.2022.113344

Abstract

Nine previously undescribed ingol-type diterpenoid polyesters with eighteen known ingol esters, two ent-atisane, and one stachane diterpenoid were isolated from the methanol extract of Euphorbia deightonii Croizat. The structures were established by extensive spectroscopic analysis involving 1D (¹H, ¹³C J-modulation) and 2D NMR experiments, HRESIMS measurements, and the comparison of the spectroscopic data with reported literature values. The cytotoxic concentrations of 13 isolated compounds were determined, and the compounds were investigated for multidrug resistance modulating activity on an L5178 mouse lymphoma cell line using a rhodamin 123 accumulation assay. Six ingol esters demonstrated the significant inhibition of P-glycoprotein, while the two ent-atisane diterpenoids were found to be inactive. The measured activities allowed to establish some structure-activity relationships. Notably, lower and higher-type diterpenoids simultaneously occurred in E. deightonii.

Keywords: Diterpenoids; Euphorbia deightonii; Euphorbiaceae; Ingol esters; Multidrug resistance reversal activity.