Novel triterpenoid pyrones, phthalimides and phthalates are selectively cytotoxic in CCRF-CEM cancer cells – Synthesis, potency, and mitochondrial mechanism of action
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F24%3A73626527" target="_blank" >RIV/61989592:15110/24:73626527 - isvavai.cz</a>
Alternative codes found
RIV/61989592:15310/24:73626527 RIV/00098892:_____/24:10158653
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S0223523424002162" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0223523424002162</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ejmech.2024.116336" target="_blank" >10.1016/j.ejmech.2024.116336</a>
Alternative languages
Result language
angličtina
Original language name
Novel triterpenoid pyrones, phthalimides and phthalates are selectively cytotoxic in CCRF-CEM cancer cells – Synthesis, potency, and mitochondrial mechanism of action
Original language description
A series of triterpenoid pyrones was synthesized and subsequently modified to introduce phthalimide or phthalate moieties into the triterpenoid skeleton. These compounds underwent in vitro cytotoxicity screening, revealing that a subset of six compounds exhibited potent activity, with IC50 values in the low micromolar range. Further biological evaluations, including Annexin V and propidium iodide staining experiment revealed, that all compounds induce selective apoptosis in cancer cells. Measurements of mitochondrial potential, cell cycle analysis, and the expression of pro- and anti-apoptotic proteins confirmed, that apoptosis was mediated via the mitochondrial pathway. These findings were further supported by cell cycle modulation and DNA/RNA synthesis studies, which indicated a significant increase in cell accumulation in the G0/G1 phase and a marked reduction in S-phase cells, alongside a substantial inhibition of DNA synthesis. The activation of caspase-3 and the cleavage of PARP, coupled with a decrease in the expression of Bcl-2 and Bcl-XL proteins, underscored the induction of apoptosis through the mitochondrial pathway. Given their high activity and pronounced effect on mitochondria function, trifluoromethyl pyrones 1f and 2f, and dihydrophthalimide 2h have been selected for further development.
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
10401 - Organic chemistry
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
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
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
ISSN
0223-5234
e-ISSN
1768-3254
Volume of the periodical
269
Issue of the periodical within the volume
APR
Country of publishing house
FR - FRANCE
Number of pages
16
Pages from-to
"116336-1"-"116336-16"
UT code for WoS article
001258464600001
EID of the result in the Scopus database
2-s2.0-85188530966