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Diterpenoids from Euphorbia royleana reverse P-glycoprotein-mediated multidrug resistance in cancer cells.
- Source :
-
Phytochemistry [Phytochemistry] 2020 Aug; Vol. 176, pp. 112395. Date of Electronic Publication: 2020 Apr 27. - Publication Year :
- 2020
-
Abstract
- Eight previously undescribed diterpenoids, euphoroyleans A-H, including two cembranes, three ingenanes, two ent-atisanes, and one ent-kaurane, along with 22 known analogues were isolated from the whole plants of Euphorbia royleana. The structures of euphoroyleans A-H, including the absolute configurations, were elucidated by extensive spectroscopic analyses, chemical transformation, and single crystal X-ray diffractions. All the isolates were screened for their chemoreversal abilities on P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) cancer cell line HepG2/DOX, and eight compounds exhibited significant activities. Among them, ingol-3,7,12-triacetate-8-benzoate, the most active MDR modulator with no obvious cytotoxicity, could enhance the efficacy of anticancer drug DOX to ca. 105 folds at 10 μM, being stronger than the positive drug verapamil. Mechanistic study revealed that ingol-3,7,12-triacetate-8-benzoate could inhibit the transport activity of P-gp rather than its expression, and the possible recognition mechanism between compounds and P-gp was predicted by molecular docking.<br />Competing Interests: Declaration of competing interest The authors declare no competing financial interest.<br /> (Copyright © 2020 Elsevier Ltd. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1873-3700
- Volume :
- 176
- Database :
- MEDLINE
- Journal :
- Phytochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 32353554
- Full Text :
- https://doi.org/10.1016/j.phytochem.2020.112395