Effect of substituents at the C3,<acute accent> C3<acute accent>N, C10 and C2-meta-benzoate positions of taxane derivatives on their activity against resistant cancer cells
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F24%3A00588228" target="_blank" >RIV/86652036:_____/24:00588228 - isvavai.cz</a>
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S0041008X24001911?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0041008X24001911?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.taap.2024.116993" target="_blank" >10.1016/j.taap.2024.116993</a>
Alternative languages
Result language
angličtina
Original language name
Effect of substituents at the C3,<acute accent> C3<acute accent>N, C10 and C2-meta-benzoate positions of taxane derivatives on their activity against resistant cancer cells
Original language description
We tested the effect of substituents at the (1) C3,<acute accent> C3<acute accent>N, (2) C10, and (3) C2-meta-benzoate positions of taxane derivatives on their activity against sensitive versus counterpart paclitaxel-resistant breast (MCF-7) and ovarian (SK-OV-3) cancer cells. We found that (1) non-aromatic groups at both C3<acute accent>and C3<acute accent>N positions, when compared with phenyl groups at the same positions of a taxane derivative, significantly reduced the resistance of ABCB1 expressing MCF-7/PacR and SK-OV-3/PacR cancer cells. This is, at least in the case of the SB-T-1216 series, accompanied by an ineffective decrease of intracellular levels in MCF-7/PacR cells. The low binding affinity of SB-T-1216 in the ABCB1 binding cavity can elucidate these effects. (2) Cyclopropanecarbonyl group at the C10 position, when compared with the H atom, seems to increase the potency and capability of the derivative in overcoming paclitaxel resistance in both models. (3) Derivatives with fluorine and methyl substituents at the C2meta-benzoate position were variously potent against sensitive and resistant cancer cells. All C2 derivatives were less capable of overcoming acquired resistance to paclitaxel in vitro than non-substituted analogs. Notably, fluorine derivatives SB-T-121205 and 121,206 were more potent against sensitive and resistant SK-OV-3 cells, and derivatives SB-T-121405 and 121,406 were more potent against sensitive and resistant MCF-7 cells. (4) The various structure-activity relationships of SB-T derivatives observed in two cell line models known to express ABCB1 favor their complex interaction not based solely on ABCB1.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Toxicology and Applied Pharmacology
ISSN
0041-008X
e-ISSN
1096-0333
Volume of the periodical
489
Issue of the periodical within the volume
AUG 2024
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
116993
UT code for WoS article
001253678700001
EID of the result in the Scopus database
2-s2.0-85195582358