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Synthesis and biological evaluation of 1-(4'-Indolyl and 6'-Quinolinyl) indoles as a new class of potent anticancer agents.

Abstract：

:A novel series of the biheterocycles-based compounds with core structure distinguished from combretastatin A-4 (1) and colchicine (5) have been synthesized and evaluated as potent anti-mitotic agents. Compound 1-(4'-Indolyl and 6'-quinolinyl)-4,5,6-trimethoxyindoles 13 and 19 showed substantial anti-proliferative activity against various human cancer cell lines, regardless to the tissue origin and the expression of multiple-drug resistance MDR1, with a mean IC(50) value of 38 and 24 nM respectively. Compound 13 (IC(50) = 1.7 μM) also exhibited similar anti-tubulin activities to 1 (IC(50) = 1.8 μM) and displayed strong binding property to the colchicine binding site on the microtubules. Computational modeling analysis revealed that the binding mechanism of compound 13 is similar to that of CA4.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Lai MJ,Chang JY,Lee HY,Kuo CC,Lin MH,Hsieh HP,Chang CY,Wu JS,Wu SY,Shey KS,Liou JP

doi

10.1016/j.ejmech.2011.04.065

subject

Has Abstract

pub_date

2011-09-01 00:00:00

pages

3623-9

issue

9

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(11)00406-5

journal_volume

46

pub_type

杂志文章

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