2. Academic Validation
  3. Toward highly potent cancer agents by modulating the C-2 group of the arylthioindole class of tubulin polymerization inhibitors

Toward highly potent cancer agents by modulating the C-2 group of the arylthioindole class of tubulin polymerization inhibitors

  • J Med Chem. 2013 Jan 10;56(1):123-49. doi: 10.1021/jm3013097.
Giuseppe La Regina 1,  Ruoli Bai,  Whilelmina Maria Rensen,  Erica Di Cesare,  Antonio Coluccia,  Francesco Piscitelli,  Valeria Famiglini,  Alessia Reggio,  Marianna Nalli,  Sveva Pelliccia,  Eleonora Da Pozzo,  Barbara Costa,  Ilaria Granata,  Amalia Porta,  Bruno Maresca,  Alessandra Soriani,  Maria Luisa Iannitto,  Angela Santoni,  Junjie Li,  Marlein Miranda Cona,  Feng Chen,  Yicheng Ni,  Andrea Brancale,  Giulio Dondio,  Stefania Vultaggio,  Mario Varasi,  Ciro Mercurio,  Claudia Martini,  Ernest Hamel,  Patrizia Lavia,  Ettore Novellino,  Romano Silvestri
Affiliations

Affiliation

  • 1 Dipartimento di Chimica e Tecnologie del Farmaco, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza Università di Roma, Piazzale Aldo Moro 5, I-00185 Roma, Italy.
PMID: 23214452 DOI: 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 IC₅₀ = 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.

Figures
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z