Flavonoid Oxime Carbamate Derivatives Reversal of Multidrug Resistance in Cancer Cells /
The effectiveness of cancer treatment has been seriously hindered by the development of multidrug resistance (MDR), mainly mediated by efflux transporters such as P‐glycoprotein (P‐gp/ABCB1). Aiming at obtaining new compounds for overcoming MDR in cancer, tangeretin ( 1 ), a natural polymethoxyflavo...
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2026
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| Sorozat: | CHEMMEDCHEM
21 No. 7 |
| Tárgyszavak: | |
| doi: | 10.1002/cmdc.202501113 |
| mtmt: | 37093174 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/40008 |
| Tartalmi kivonat: | The effectiveness of cancer treatment has been seriously hindered by the development of multidrug resistance (MDR), mainly mediated by efflux transporters such as P‐glycoprotein (P‐gp/ABCB1). Aiming at obtaining new compounds for overcoming MDR in cancer, tangeretin ( 1 ), a natural polymethoxyflavonoid, was derivatized. After obtaining the corresponding oxime ( 2 ), a set of 23 novel oxime carbamates ( 3 – 26 ) was prepared via carbonyldiimidazole‐mediated reaction with various amines or by reaction with isocyanates. Their structures were assigned mainly by 1D and 2D NMR experiments. The compounds ( 1–26 ) were evaluated for their MDR reversal potential, using the rhodamine‐123 accumulation assay and chemosensitivity experiments, in human ABCB1 ‐gene transfected L5178Y mouse lymphoma cells. A significant increase in P‐gp inhibitory activity was observed for most of the derivatives at noncytotoxic concentrations. Notably, compounds 19 , 20 , and 22 , bearing an aliphatic substituent, were the most active, exhibiting a strong MDR reversal effect at 2 μM. Moreover, drug combination assays revealed that most of the derivatives were able to synergize doxorubicin. Selected compounds were also tested in the ATPase assay, where most of them acted as inhibitors. |
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| Terjedelem/Fizikai jellemzők: | 14 |
| ISSN: | 1860-7179 |