Synthesis and Biological Evaluation of Small Molecular Compounds as Potent Antimitotic/Vascular Disrupting Agents

CNU IR > Pharmacy and Science > 2011 Taiwanese-Russian Organic, Medicinal and Bio Chemistry Interactions & PST Medicinal Chemistry Symposium > Item 310902800/24208

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Title:	Synthesis and Biological Evaluation of Small Molecular Compounds as Potent Antimitotic/Vascular Disrupting Agents
Authors:	Jing-Ping Liou (劉景平)
Date:	2011
Issue Date:	2011-06-23 14:57:02 (UTC+8)
Abstract:	A series of aroylquinoline derivatives ([6,6]-fused heterocycle) were synthesized and evaluated for anticancer activity. 5-Amino-6-methoxy-2-aroylquinoline 15 showed more potent antiproliferative activity (IC50 values ranging from 0.2 to 0.4 nM) as compared to combretastatin A-4 (CA4, IC50 = 1.9-835 nM) against various human cancer cell lines and a MDR-resistant cancer cell line. Compound 15 (IC50 = 1.6 μM) exhibited more potent inhibition of tubulin polymerization than CA4 (IC50 - 2.1 μM) and showed strong binding property to the colchicine binding site of microtubules. In an attempt to mimic the 3,4,5-trimethoxyphenyl-Z-stilbene moiety of combretastatin A-4, a series of N-aryl-5,6,7-trimethoxyindoldes ([6,5]-fused tieterocycle) were synthesized via copper-catalyzed Ullmann-tyfype N-aryarylation through corresponding 5,6,7-trimethoxyindole and aryl halides. These synthesized compounds demonstrated potent antiproliferative activity providing a novel skeleton for potent tubulin polymerization inhibitors. Compound 6 demonstrated substantial vascular disrupting activity (VDA), which was capable to disrupt formed capillaries in concacentration-dependent manner without affecting cell viability.
Relation:	2011年台俄有機、藥物與生物化學交流暨藥物化學研討會，起迄日：2011/04/06~2011/04/05，地點：溪頭台大實驗林
Appears in Collections:	[Pharmacy and Science] 2011 Taiwanese-Russian Organic, Medicinal and Bio Chemistry Interactions & PST Medicinal Chemistry Symposium

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