Lycorine Carbamate Derivatives for Reversing P-Glycoprotein-Mediated Multidrug Resistance in Human Colon Adenocarcinoma Cells
Multidrug resistance (MDR) is a major challenge in cancer chemotherapy. Aiming at generating a small library of anticancer compounds for overcoming MDR, lycorine (1), a major Amaryllidaceae alkaloid isolated from Pancratium maritimum, was derivatized. Thirty-one new compounds (2–32) were obtained by...
Elmentve itt :
| Szerzők: | |
|---|---|
| Dokumentumtípus: | Cikk |
| Megjelent: |
2023
|
| Sorozat: | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
24 No. 3 |
| Tárgyszavak: | |
| doi: | 10.3390/ijms24032061 |
| mtmt: | 33578997 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/26281 |
| LEADER | 02329nab a2200265 i 4500 | ||
|---|---|---|---|
| 001 | publ26281 | ||
| 005 | 20230123082846.0 | ||
| 008 | 230123s2023 hu o 0|| Angol d | ||
| 022 | |a 1661-6596 | ||
| 024 | 7 | |a 10.3390/ijms24032061 |2 doi | |
| 024 | 7 | |a 33578997 |2 mtmt | |
| 040 | |a SZTE Publicatio Repozitórium |b hun | ||
| 041 | |a Angol | ||
| 100 | 1 | |a Sancha Shirley A. R. | |
| 245 | 1 | 0 | |a Lycorine Carbamate Derivatives for Reversing P-Glycoprotein-Mediated Multidrug Resistance in Human Colon Adenocarcinoma Cells |h [elektronikus dokumentum] / |c Sancha Shirley A. R. |
| 260 | |c 2023 | ||
| 300 | |a 23 | ||
| 490 | 0 | |a INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES |v 24 No. 3 | |
| 520 | 3 | |a Multidrug resistance (MDR) is a major challenge in cancer chemotherapy. Aiming at generating a small library of anticancer compounds for overcoming MDR, lycorine (1), a major Amaryllidaceae alkaloid isolated from Pancratium maritimum, was derivatized. Thirty-one new compounds (2–32) were obtained by chemical transformation of the hydroxyl groups of lycorine into mono- and di-carbamates. Compounds 1–32 were evaluated as MDR reversers, through the rhodamine-123 accumulation assay by flow cytometry and chemosensitivity assays, in resistant human colon adenocarcinoma cancer cells (Colo 320), overexpressing P-glycoprotein (P-gp, ABCB1). Significant inhibition of P-gp efflux activity was observed for the di-carbamate derivatives, mainly those containing aromatic substituents, at non-cytotoxic concentrations. Compound 5, bearing a benzyl substituent, and compounds 9 and 25, with phenethyl moieties, were among the most active, exhibiting strong inhibition at 2 µM, being more active than verapamil at 10-fold higher concentration. In drug combination assays, most compounds were able to synergize doxorubicin. Moreover, some derivatives showed a selective antiproliferative effect toward resistant cells, having a collateral sensitivity effect. In the ATPase assay, selected compounds (2, 5, 9, 19, 25, and 26) were shown to behave as inhibitors. | |
| 650 | 4 | |a Általános orvostudomány | |
| 650 | 4 | |a Egészségtudományok | |
| 700 | 0 | 1 | |a Szemerédi Nikoletta |e aut |
| 700 | 0 | 1 | |a Spengler Gabriella |e aut |
| 700 | 0 | 1 | |a Ferreira Maria-José U. |e aut |
| 856 | 4 | 0 | |u http://publicatio.bibl.u-szeged.hu/26281/1/SG_ijms-24-02061.pdf |z Dokumentum-elérés |