title: A novel C,D-spirolactone analogue of paclitaxel: autophagy instead of apoptosis as a previously unknown mechanism of cytotoxic action for taxoids.
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.
authors.affiliation: Faculty of Chemistry, University of Belgrade, Studentski trg 16, 11158 Belgrade, 118 P. O. B. 51 PAC, 105305, Serbia.
authors.forename: Milena V
authors.initials: MV
authors.lastname: Trmcic
authors.forename: Radomir V
authors.initials: RV
authors.lastname: Matovic
authors.forename: Gordana I
authors.initials: GI
authors.lastname: Tovilovic
authors.forename: Biljana Z
authors.initials: BZ
authors.lastname: Ristic
authors.forename: Vladimir S
authors.initials: VS
authors.lastname: Trajkovic
authors.forename: Zorana B
authors.initials: ZB
authors.lastname: Ferjancic
authors.forename: Radomir N
authors.initials: RN
authors.lastname: Saicic
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D006801:Humans; D015394:Molecular Structure; D017239:Paclitaxel / Q000737:chemistry* / Q000494:pharmacology; D013148:Spironolactone / Q000031:analogs & derivatives*
chemical_list: D013148:Spironolactone; D017239:Paclitaxel