A novel C,D-spirolactone analogue of paclitaxel: autophagy instead of apoptosis as a previously unknown mechanism of cytotoxic action for taxoids
2012
Autori:
Trmčić, Milena V.Matović, Radomir V.
Tovilović-Kovačević, Gordana
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Ristić, Biljana Z.
Trajković, Vladimir S.
Ferjančić, Zorana B.
Saičić, Radomir N.
Tip dokumenta:
Članak u časopisu (Objavljena verzija)
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© 2012 by The Royal Society of Chemistry
Metapodaci
Prikaz svih podataka o dokumentuApstrakt:
The design, synthesis and biological evaluation of a novel C,D-spirolactone analogue of paclitaxel is described. This is the first paclitaxel analogue without an oxetane D-ring that shows a significant cytotoxic effect (activity one order of magnitude lower than paclitaxel). More importantly, its cytotoxicity is a result of a different mechanism of action, involving mTOR inhibition-dependent autophagy instead of G2/M cell cycle arrest-dependent apoptosis.
Ključne reči:
C,D-spirolactone derivatives; Paclitaxel; Cytotoxic; Autophagy; mTOR inhibitionIzvor:
Organic and Biomolecular Chemistry, 2012, 10, 25, 4933-4942Finansiranje / projekti:
- Razvoj novih sintetičkih metoda i njihova primena u sintezi prirodnih proizvoda i biološki aktivnih jedinjenja (RS-MESTD-Basic Research (BR or ON)-172027)
- Modulacija signalnih puteva koji kontrolišu intracelularni energetski balans u terapiji tumora i neuro-imuno-endokrinih poremećaja (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41025)
DOI: 10.1039/c2ob25514f
ISSN: 1477-0520
PubMed: 22614284