2-Hydroxy-3,4,5-trimethoxybenzophenones (8-16) manifest pseudo-ring formation involving intramolecular hydrogen bonding of the 2-OH and the carbonyl group. Among the synthetic products described in this report, (3-hydroxy-4-methoxyphenyl)(2-hydroxy-3,4,5-trimethoxyphenyl)-methanone (14) and (3-amino-4-methoxyphenyl)(2-hydroxy-3,4,5-trimethoxy-phenyl)methanone (16) exhibit significant antiproliferative activity against KB cells with IC 50 values of 11.1 and 11.3 nM, respectively. These two compounds also displayed tubulin affinity comparable to that of combretastatin A-4. In studies with human umbilical vein endothelial cells, compounds 14 and 16 revealed concentration-dependent vascular-disrupting properties. The results support the rationale of the pseudo-ring concept and suggest further investigation of A-ring modification in these benzophenones.
|Number of pages||9|
|Journal||European Journal of Medicinal Chemistry|
|Publication status||Published - Apr 22 2014|
- Vascular-disrupting agents
ASJC Scopus subject areas
- Drug Discovery
- Organic Chemistry