Title: Toward highly potent cancer agents by modulating the C-2 group of the arylthioindole class of tubulin polymerization inhibitors
Authors: La Regina, Giuseppe
Bai, Ruoli
Rensen, Whilelmina Maria
Di Cesare, Erica
Coluccia, Antonio
Piscitelli, Francesco
Famiglini, Valeria
Reggio, Alessia
Nalli, Marianna
Pelliccia, Sveva
Da Pozzo, Eleonora
Costa, Barbara
Granata, Ilaria
Porta, Amalia
Maresca, Bruno
Soriani, Alessandra
Iannitto, Maria Luisa
Santoni, Angela
Li, Junjie
Miranda Cona, Marlein
Chen, Feng
Ni, Yicheng
Brancale, Andrea
Dondio, Giulio
Vultaggio, Stefania
Varasi, Mario
Mercurio, Ciro
Martini, Claudia
Hamel, Ernest
Lavia, Patrizia
Novellino, Ettore
Silvestri, Romano # ×
Issue Date: Jan-2013
Publisher: ACS Publications
Series Title: Journal of Medicinal Chemistry vol:56 issue:1 pages:123-149
Article number: 10.1021/jm3013097
Abstract: New arylthioindole derivatives having different cyclic substituents at position 2 of the indole were synthesized as anticancer agents. Several compounds inhibited tubulin polymerization at submicromolar concentration and inhibited cell growth at low nanomolar concentrations. Compounds 18 and 57 were superior to the previously synthesized 5. Compound 18 was exceptionally potent as an inhibitor of cell growth: it showed IC(50) = 1.0 nM in MCF-7 cells, and it was uniformly active in the whole panel of cancer cells and superior to colchicine and combretastatin A-4. Compounds 18, 20, 55, and 57 were notably more potent than vinorelbine, vinblastine, and paclitaxel in the NCI/ADR-RES and Messa/Dx5 cell lines, which overexpress P-glycoprotein. Compounds 18 and 57 showed initial vascular disrupting effects in a tumor model of liver rhabdomyosarcomas at 15 mg/kg intravenous dosage. Derivative 18 showed water solubility and higher metabolic stability than 5 in human liver microsomes.
ISSN: 0022-2623
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Theragnostic Laboratory (+)
× corresponding author
# (joint) last author

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