Epoxylathyrol Derivatives Modulation of ABCB1-Mediated Multidrug Resistance in Human Colon Adenocarcinoma and Mouse T-Lymphoma Cells /
Epoxyboetirane A (1), a macrocyclic diterpene that was found to be inactive as an ABCB1 modulator, was submitted to several chemical transformations, aimed at generating a series of compounds with improved multidrug resistance (MDR)-modifying activity. Overall, 23 new derivatives were prepared, in a...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2015
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| Sorozat: | JOURNAL OF NATURAL PRODUCTS
78 No. 9 |
| doi: | 10.1021/acs.jnatprod.5b00370 |
| mtmt: | 2951177 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/10421 |
| LEADER | 02430nab a2200277 i 4500 | ||
|---|---|---|---|
| 001 | publ10421 | ||
| 005 | 20190606145422.0 | ||
| 008 | 170202s2015 hu o 0|| zxx d | ||
| 022 | |a 0163-3864 | ||
| 024 | 7 | |a 10.1021/acs.jnatprod.5b00370 |2 doi | |
| 024 | 7 | |a 2951177 |2 mtmt | |
| 040 | |a SZTE Publicatio Repozitórium |b hun | ||
| 041 | |a zxx | ||
| 100 | 1 | |a Matos Ana M. | |
| 245 | 1 | 0 | |a Epoxylathyrol Derivatives |h [elektronikus dokumentum] : |b Modulation of ABCB1-Mediated Multidrug Resistance in Human Colon Adenocarcinoma and Mouse T-Lymphoma Cells / |c Matos Ana M. |
| 260 | |c 2015 | ||
| 300 | |a 2215-2228 | ||
| 490 | 0 | |a JOURNAL OF NATURAL PRODUCTS |v 78 No. 9 | |
| 520 | 3 | |a Epoxyboetirane A (1), a macrocyclic diterpene that was found to be inactive as an ABCB1 modulator, was submitted to several chemical transformations, aimed at generating a series of compounds with improved multidrug resistance (MDR)-modifying activity. Overall, 23 new derivatives were prepared, in addition to the already reported epoxylathyrol (2) and methoxyboetirol (3). Their anti-MDR potential was assessed through both functional and chemosensitivity assays on resistant human colon adenocarcinoma and human ABCB1-gene transfected L5178Y mouse lymphoma cells. Structure-activity relationship analysis showed that different substitution patterns led to distinct ABCB1 inhibitory activities, although intrinsic cellular characteristics seemed to influence the modulatory behavior. A considerable enhancement in MDR-modifying activity was observed for aromatic compounds in both cell lines, particularly in 3,17-disubstituted esters derived from 3, a Payne-rearranged Michael adduct of 2. All compounds tested were revealed to interact synergistically with doxorubicin, and ATPase inhibition by three representative MDR-modifying compounds was also investigated. On account of its outstanding ABCB1 inhibitory activity at 0.2 muM and overall remarkable bioactive profile, methoxyboetirane B (22) was found to be a new promising lead for MDR-reversing anticancer drug development. | |
| 700 | 0 | 1 | |a Reis Mariana |e aut |
| 700 | 0 | 1 | |a Duarte Noélia |e aut |
| 700 | 0 | 1 | |a Spengler Gabriella |e aut |
| 700 | 0 | 1 | |a Molnár József |e aut |
| 700 | 0 | 1 | |a Ferreira Maria-Jose U. |e aut |
| 856 | 4 | 0 | |u http://publicatio.bibl.u-szeged.hu/10421/1/J__NatProd_u.pdf |z Dokumentum-elérés |
| 856 | 4 | 0 | |u http://publicatio.bibl.u-szeged.hu/10421/7/acs.jnatprod.5b00370.pdf |z Dokumentum-elérés |