Synthesis and biological evaluation of 1-(4'-Indolyl and 6'-Quinolinyl) indoles as a new class of potent anticancer agents
- Eur J Med Chem. 2011 Sep;46(9):3623-9. doi: 10.1016/j.ejmech.2011.04.065.
- 1. School of Pharmacy, College of Pharmacy, Taipei Medical University, No 250, Wuxing Street, Taipei 11031, Taiwan, ROC.
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.