Arylthioindoles, potent inhibitors of tubulin polymerization.
Several arylthioindoles had excellent activity as inhibitors both of tubulin polymerization and of the growth of MCF-7 human breast carcinoma cells. Methyl 3-[(3,4,5-trimethoxyphenyl)thio]-5-methoxy-1H-indole-2-carboxylate (21), the most potent derivative, showed IC(50) = 2.0 microM, 1.6 times more active than colchicine and about as active as combretastatin A-4 (CSA4). Compound 21 inhibited the growth of the MCF-7 cells at IC(50) = 13 nM. Colchicine and CSA4 had 13 nM and 17 nM IC(50) values, respectively, with these cells.
De Martino
Gabriella
G
Dipartimento di Studi Farmaceutici, Università di Roma, La Sapienza, I-00185 Rome, Italy.
La Regina
Giuseppe
G
Coluccia
Antonio
A
Edler
Michael C
MC
Barbera
Maria Chiara
MC
Brancale
Andrea
A
Wilcox
Elizabeth
E
Hamel
Ernest
E
Artico
Marino
M
Silvestri
Romano
R
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001704:Biopolymers; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D003864:Depression, Chemical; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D013440:Sulfides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014404:Tubulin / Q000737:chemistry*; D050257:Tubulin Modulators
D000970:Antineoplastic Agents; D001704:Biopolymers; D007211:Indoles; D013440:Sulfides; D014404:Tubulin; D050257:Tubulin Modulators