Triterpenoid phthalimides as selective anti-cancer agents targeting mitochondrial apoptosis
Jazyk angličtina Země Francie Médium print-electronic
Typ dokumentu časopisecké články
PubMed
39673861
DOI
10.1016/j.ejmech.2024.117126
PII: S0223-5234(24)01008-0
Knihovny.cz E-zdroje
- Klíčová slova
- Apoptosis, Betulin, Betulinic acid, Cancer, Cell cycle regulation, Diels-Alder reaction, Mitochondria, Phthalates, Triterpenoids, Wittig reaction,
- MeSH
- apoptóza * účinky léků MeSH
- ftalimidy * farmakologie chemie chemická syntéza MeSH
- lidé MeSH
- mitochondrie * účinky léků metabolismus MeSH
- molekulární struktura MeSH
- nádorové buněčné linie MeSH
- proliferace buněk * účinky léků MeSH
- protinádorové látky * farmakologie chemie chemická syntéza MeSH
- screeningové testy protinádorových léčiv * MeSH
- triterpeny * farmakologie chemie chemická syntéza MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- ftalimidy * MeSH
- protinádorové látky * MeSH
- triterpeny * MeSH
Starting from benzyl 30-oxobetulinate and 30-oxobetulin diacetate, substituted dienes were synthesized and subjected to Diels-Alder reaction, yielding a variety of triterpenoid phthalates, phthalimides, and related derivatives. A total of 55 new compounds were prepared and tested for in vitro cytotoxic activity against eight cancer cell lines and two non-cancerous cell lines. Four compounds with IC50 values of 5 μM or lower were selected for further investigation. These compounds induced apoptosis in CCRF-CEM cells in a concentration-dependent manner, accompanied by mitochondrial depolarization and altered expression of key proteins involved in mitochondrial apoptosis. The compounds also disrupted DNA replication and transcriptional activity. Modulation of key proliferation pathways, including PI3K/Akt and STAT3, further supported the antiproliferative potential of these derivatives. Considering their high cytotoxicity and antiproliferative activity in CCRF-CEM cells, compounds 19, 26, 28, and 30 have been identified as promising candidates for further development.
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