Ingol diterpenoids as P-glycoprotein-dependent multidrug resistance (MDR) reversal agents from Euphorbia marginata
| Autor: | Jun Sang, Jia-Qi Chen, Yi-Jing Tian, Run-Zhu Fan, Yao Zhang, Gui-Hua Tang, Sheng Yin |
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| Rok vydání: | 2019 |
| Předmět: |
Pharmacology
Crystallography X-Ray 01 natural sciences Biochemistry Euphorbia Drug Discovery Humans MDR Modulators ATP Binding Cassette Transporter Subfamily B Member 1 Molecular Biology P-glycoprotein biology 010405 organic chemistry Chemistry Spectrum Analysis Organic Chemistry Hep G2 Cells biology.organism_classification Anticancer drug Drug Resistance Multiple 0104 chemical sciences Multiple drug resistance 010404 medicinal & biomolecular chemistry biology.protein Cancer cell lines Diterpenes |
| Zdroj: | Bioorganic chemistry. 95 |
| ISSN: | 1090-2120 |
| Popis: | Twenty new ingol diterpenoids, euphornans A–T (1–20), representing a rare class of C-19-oxidated and H-2, H-3 β-oriented ingols, were isolated from the seeds of Euphorbia marginata. Their structures including absolute configurations were elucidated by extensive spectroscopic analysis, ECD analysis, and single crystal X-ray diffraction. Compounds 1–20 were screened for the multidrug resistance (MDR) reversal activity on P-glycoprotein (Pgp)-dependent MDR cancer cell line HepG2/ADR, and 11, 14, and 18 were identified as potent MDR modulators that could enhance the efficacy of anticancer drug adriamycin to ca. 20 folds at 5 μM. The Pgp inhibition mechanism and brief structure–activity relationships (SARs) of these compounds were also discussed. |
| Databáze: | OpenAIRE |
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