Celastraceae sesquiterpenoids: biological activity and synthesis

Spivey, Alan C.; Weston, Matthew; Woodhead, Steven J.

doi:10.1039/b000678p

Cited by 177 publications

(151 citation statements)

References 43 publications

Supporting

Mentioning

149

Contrasting

Unclassified

Order By: Relevance

“…Among the active compounds identified in those extracts are sesquiterpenes, which constitute a wide family of natural compounds with a considerable range of bioactive properties and with potential clinical applications as anticancer drugs, and MDR reversal agents in cancer cells (16) and in the protozoan parasite Leishmania (17,18). Because of these previous findings, we have initiated research to determine the cellular target(s) for sesquiterpenes and to characterize their molecular mechanism of action to rationally design new, more efficient modulators based on their chemical structure.…”

Section: Introductionmentioning

confidence: 99%

Celastraceae Sesquiterpenes as a New Class of Modulators That Bind Specifically to Human P-Glycoprotein and Reverse Cellular Multidrug Resistance

Muñoz-Martínez

Cortés-Selva

et al. 2004

Cancer Research

View full text Add to dashboard Cite

Overexpression of ABCB1 (MDR1) P-glycoprotein, a multidrug efflux pump, is one mechanism by which tumor cells may develop multidrug resistance (MDR), preventing the successful chemotherapeutic treatment of cancer. Sesquiterpenes from Celastraceae family are natural compounds shown previously to reverse MDR in several human cancer cell lines and Leishmania strains. However, their molecular mechanism of reversion has not been characterized. In the present work, we have studied the ability of 28 dihydro-␤-agarofuran sesquiterpenes to reverse the P-glycoprotein-dependent MDR phenotype and elucidated their molecular mechanism of action. Cytotoxicity assays using human MDR1-transfected NIH-3T3 cells allowed us to select the most potent sesquiterpenes reversing the in vitro resistance to daunomycin and vinblastine. Flow cytometry experiments showed that the above active compounds specifically inhibited drug transport activity of P-glycoprotein in a saturable, concentration-dependent manner (K i down to 0.24 ؎ 0.01 mol/L) but not that of ABCC1 (multidrug resistance protein 1; MRP1), ABCC2 (MRP2), and ABCG2 (breast cancer resistance protein; BCRP) transporters. Moreover, sesquiterpenes inhibited at submicromolar concentrations the P-glycoprotein-mediated transport of [ 3 H]colchicine and tetramethylrosamine in plasma membrane from CH R B30 cells and P-glycoproteinenriched proteoliposomes, supporting that P-glycoprotein is their molecular target. Photoaffinity labeling in plasma membrane and fluorescence spectroscopy experiments with purified protein suggested that sesquiterpenes interact with transmembrane domains of P-glycoprotein. Finally, sesquiterpenes modulated P-glycoprotein ATPase-activity in a biphasic, concentration-dependent manner: they stimulated at very low concentrations but inhibited ATPase activity as noncompetitive inhibitors at higher concentrations. Sesquiterpenes from Celastraceae are promising P-glycoprotein modulators with potential applications in cancer chemotherapy because of their MDR reversal potency and specificity for P-glycoprotein.

show abstract

Section: Introductionmentioning

confidence: 99%

Celastraceae Sesquiterpenes as a New Class of Modulators That Bind Specifically to Human P-Glycoprotein and Reverse Cellular Multidrug Resistance

Muñoz-Martínez

Cortés-Selva

et al. 2004

Cancer Research

View full text Add to dashboard Cite

show abstract

“…It has been shown that sesquiterpenes from the Celastraceae and Euphorbiaceae families could act as reversal agents (Spivey et al, 2002;Madureira et al, 2004). The probable mechanism of feselol action could be its interaction with and inhibition of the function of the MRP2.…”

Section: Discussionmentioning

confidence: 99%

Feselol Enhances the Cytotoxicity and DNA Damage Induced by Cisplatin in 5637 Cells

Mollazadeh

Matin

Bahrami

et al. 2011

Zeitschrift Für Naturforschung C

View full text Add to dashboard Cite

Transitional cell carcinoma (TCC), which is the most common type of bladder cancer, shows resistance to chemotherapeutic agents due to the overexpression of drug effl ux pumps. In this study, the effects of feselol, a sesquiterpene coumarin extracted from Ferula badrakema, on cisplatin cytotoxicity were investigated in 5637 cells, a TCC subline. Cell viability and DNA lesion were evaluated by thiazolyl blue tetrazolium bromide and comet assays, respectively. Feselol had no signifi cant cytotoxic effect in 5637 cells but at 32 μg/mL it increased the cytotoxicity of 1 μg/mL cisplatin by 37% after 24 h. Furthermore, the comet assay revealed that DNA damage induced by cisplatin in 5637 cells is enhanced by 31% when used in combination with feselol. Therefore, feselol might be considered as an effective reversal agent for future in vivo and clinical studies.

show abstract

“…Its phytochemistry has been examined and it is known to contain multiple constituents including flavonoids, tannins, alkaloids, triterpenes and sesquiterpenes. 2,12,[32][33][34] However, some studies have shown fatal outcomes after intake of medicinal plants with drugs. For example, concomitant use of warfarin and plants such as ginkgo biloba and ginseng are contraindicated in order to reduce the number of deaths by bleeding.…”

Section: Introductionmentioning

confidence: 99%

Study on the temperature, respiratory rate, heart rate and electrocardiogram of concomitant administration of Maytenus macrocarpa “Chuchuhuasi” and Propranolol in escalating doses

Zambrano-Huailla¹,

Zambrano-Huailla²,

Karelya³

et al. 2016

View full text Add to dashboard Cite

Background: Previous studies of Maytenus macrocarpa "Chuchuhuasi" and linked species have corroborated their biological effects related to cardiovascular, respiratory, and others systems. This research has focused on evaluating the effect in the corporeal temperature, respiratory rate, heart rate and electrocardiogram of concomitant administration of "Chuchuhuasi" and propranolol in escalating doses. Methods: Albino rats were divided randomly into four control groups and five experimental groups. Temperature was measured by a digital thermometer, respiratory rate by direct-counting and electrocardiogram and heart rate by a Grass Polygraph. Rhythmic and arrhythmic electrocardiographic patterns were identified by a mathematical modeling of autocorrelation. The outcomes were acquired in periods of time but were analyzed using the average of the whole of the experiment. The result was applied to the following statistical tests: one-way ANOVA, Tuckey, Shapiro-Wilk, Pearson Correlation and Chi square with Yate's correction test. Results: The comparison between control and experimental groups showed a profile of raise in the corporeal temperature, then, for the respiratory rate the bias was to increase, in contrast, it was showed trend to decrease of the heart rate and an increase of voltages of p and r wave, also, an increment of p-r interval and presences of arrhythmias. Conclusion: This study revealed effects of concomitant administration of propranolol and Maytenus macrocarpa on temperature, respiratory rate, heart rate and electrocardiogram. In addition, it showed abnormalities in the electrocardiogram which were associated with arrhythmia patterns Thus, the usage of propranolol and Maytenus macrocarpa may negatively impact several aspects of the health of users of these drugs.

show abstract

Celastraceae sesquiterpenoids: biological activity and synthesis

Cited by 177 publications

References 43 publications

Celastraceae Sesquiterpenes as a New Class of Modulators That Bind Specifically to Human P-Glycoprotein and Reverse Cellular Multidrug Resistance

Celastraceae Sesquiterpenes as a New Class of Modulators That Bind Specifically to Human P-Glycoprotein and Reverse Cellular Multidrug Resistance

Feselol Enhances the Cytotoxicity and DNA Damage Induced by Cisplatin in 5637 Cells

Study on the temperature, respiratory rate, heart rate and electrocardiogram of concomitant administration of Maytenus macrocarpa “Chuchuhuasi” and Propranolol in escalating doses

Contact Info

Product

Resources

About