TY - JOUR
T1 - Antimitotic and vascular disrupting agents
T2 - 2-Hydroxy-3,4,5- trimethoxybenzophenones
AU - Chang, Chih Yi
AU - Chuang, Hsun Yueh
AU - Lee, Hsueh Yun
AU - Yeh, Teng Kuang
AU - Kuo, Ching Chuan
AU - Chang, Chi Yen
AU - Chang, Jang Yang
AU - Liou, Jing Ping
N1 - Funding Information:
This research were supported by the National Science Council of the Republic of China (grant no. NSC 100-2628-M-038-001-MY3 , and NSC 101-2325-B-038-002 ).
PY - 2014/4/22
Y1 - 2014/4/22
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ejmech.2014.02.061
DO - 10.1016/j.ejmech.2014.02.061
M3 - Article
C2 - 24657567
AN - SCOPUS:84896536146
VL - 77
SP - 306
EP - 314
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
SN - 0223-5234
ER -