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Effective MDR reversers through phytochemical study of Euphorbia boetica
Author(s) -
Neto Sara,
Duarte Noélia,
Pedro Cecília,
Spengler Gabriella,
Molnár Joséph,
Ferreira MariaJosé U.
Publication year - 2019
Publication title -
phytochemical analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.574
H-Index - 72
eISSN - 1099-1565
pISSN - 0958-0344
DOI - 10.1002/pca.2841
Subject(s) - chemistry , phytochemical , multiple drug resistance , acylation , euphorbia , chromatography , stereochemistry , organic chemistry , biochemistry , traditional medicine , medicine , antibiotics , catalysis
Macrocyclic diterpenes from Euphorbia species were found to be promising modulators of multidrug resistance (MDR), a complex phenomenon that hampers the effectiveness of cancer therapy. Objective To find new effective MDR reversers through the phytochemical study of E. boetica , including isolation and molecular derivatisation. Material and methods The phytochemical study of E. boetica was performed through chromatographic techniques. Preliminary analysis of crude chromatographic fractions from the methanol extract was carried out by 1 H‐NMR in order to prioritise the study of those having macrocyclic diterpenes. Polyamide resin was used to remove chlorophylls. Molecular derivatisation of isolated compounds comprised hydrolysis, reduction and acylation reactions. The structural identification of compounds was performed through analysis of spectroscopic data, mainly one‐dimensional‐ and two‐dimensional‐NMR. The MDR reversing activity was assessed using a combination of transport and chemosensitivity assays, in mouse lymphoma (L5178Y‐MDR) and Colo320 cell models. Results The 1 H‐NMR study of crude fractions and application of a straightforward method to remove chlorophylls, allowed the effortless isolation of two lathyrane‐type diterpenes in large amounts, including the new polyester, euphoboetirane B ( 1 ). Taking advantage of the chemical functions of 1 , 13 new derivatives were prepared. Several compounds showed to be promising modulators of P‐glycoprotein (P‐gp), in resistant cancer cells. Most of the compounds tested revealed to interact synergistically with doxorubicin. Conclusion These results corroborate the importance of macrocyclic lathyrane diterpenes as effective lead compounds for the reversal of MDR.