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A novel C,D-spirolactone analogue of paclitaxel: autophagy instead of apoptosis as a previously unknown mechanism of cytotoxic action for taxoids

Authorized Users Only
2012
Authors
Trmcic, Milena V.
Matović, Radomir
Tovilović, Gordana
Ristic, Biljana Z.
Trajković, Vladimir
Ferjančić, Zorana
Saičić, Radomir N.
Article (Published version)
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Abstract
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 G(2)/M cell cycle arrest-dependent apoptosis.
Source:
Organic & Biomolecular Chemistry, 2012, 10, 25, 4933-4942
Publisher:
  • Royal Soc Chemistry, Cambridge
Projects:
  • The development of new synthetic methods and their application in the synthesis of natural products and biologically active molecules (RS-172027)
  • Modulation of intracellular energy balance-controlling signalling pathways in therapy of cancer and neuro-immuno-endocrine disorders (RS-41025)

DOI: 10.1039/c2ob25514f

ISSN: 1477-0520

PubMed: 22614284

WoS: 000304885200015

Scopus: 2-s2.0-84862224265
[ Google Scholar ]
11
12
URI
http://cer.ihtm.bg.ac.rs/handle/123456789/981
Collections
  • Radovi istraživača / Researchers' publications
Institution
IHTM
TY  - JOUR
AU  - Trmcic, Milena V.
AU  - Matović, Radomir
AU  - Tovilović, Gordana
AU  - Ristic, Biljana Z.
AU  - Trajković, Vladimir
AU  - Ferjančić, Zorana
AU  - Saičić, Radomir N.
PY  - 2012
UR  - http://cer.ihtm.bg.ac.rs/handle/123456789/981
AB  - 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 G(2)/M cell cycle arrest-dependent apoptosis.
PB  - Royal Soc Chemistry, Cambridge
T2  - Organic & Biomolecular Chemistry
T1  - A novel C,D-spirolactone analogue of paclitaxel: autophagy instead of apoptosis as a previously unknown mechanism of cytotoxic action for taxoids
VL  - 10
IS  - 25
SP  - 4933
EP  - 4942
DO  - 10.1039/c2ob25514f
ER  - 
@article{
author = "Trmcic, Milena V. and Matović, Radomir and Tovilović, Gordana and Ristic, Biljana Z. and Trajković, Vladimir and Ferjančić, Zorana and Saičić, Radomir N.",
year = "2012",
url = "http://cer.ihtm.bg.ac.rs/handle/123456789/981",
abstract = "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 G(2)/M cell cycle arrest-dependent apoptosis.",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "Organic & Biomolecular Chemistry",
title = "A novel C,D-spirolactone analogue of paclitaxel: autophagy instead of apoptosis as a previously unknown mechanism of cytotoxic action for taxoids",
volume = "10",
number = "25",
pages = "4933-4942",
doi = "10.1039/c2ob25514f"
}
Trmcic MV, Matović R, Tovilović G, Ristic BZ, Trajković V, Ferjančić Z, Saičić RN. A novel C,D-spirolactone analogue of paclitaxel: autophagy instead of apoptosis as a previously unknown mechanism of cytotoxic action for taxoids. Organic & Biomolecular Chemistry. 2012;10(25):4933-4942
Trmcic, M. V., Matović, R., Tovilović, G., Ristic, B. Z., Trajković, V., Ferjančić, Z.,& Saičić, R. N. (2012). A novel C,D-spirolactone analogue of paclitaxel: autophagy instead of apoptosis as a previously unknown mechanism of cytotoxic action for taxoids.
Organic & Biomolecular ChemistryRoyal Soc Chemistry, Cambridge., 10(25), 4933-4942.
https://doi.org/10.1039/c2ob25514f
Trmcic Milena V., Matović Radomir, Tovilović Gordana, Ristic Biljana Z., Trajković Vladimir, Ferjančić Zorana, Saičić Radomir N., "A novel C,D-spirolactone analogue of paclitaxel: autophagy instead of apoptosis as a previously unknown mechanism of cytotoxic action for taxoids" 10, no. 25 (2012):4933-4942,
https://doi.org/10.1039/c2ob25514f .

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