New ethacrynic acid derivatives as potent cytoskeletal modulators in trabecular meshwork cells.
A series of ethacrynic acid (ECA) derivatives were synthesized and examined for ocular hypotensive activity. Efficacy was evaluated in a cell-shape assay, using human trabecular meshwork cells, and cytotoxicity in a (3-(4,5-dimethylthiazole-2-yl)-5-(3-carboxymethoxy phenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay, using cultured bovine trabecular meshwork cells. Many of the derivatives demonstrated efficacy equal to or greater than that of ECA. SA9000 was selected as the most promising candidate for a novel ocular hypotensive drug with few side effects.
Shimazaki
Atsushi
A
Research and Development Center, Santen Pharmaceutical Co. Ltd., Takayama, Ikoma, Japan. shimazaki@snaten.co.jp
Suhara
Hiroshi
H
Ichikawa
Masaki
M
Matsugi
Takeshi
T
Konomi
Koji
K
Takagi
Yasutaka
Y
Hara
Hideaki
H
Rao
Ponugoti Vasantha
PV
Epstein
David Lee
DL
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects* / Q000502:physiology; D004976:Ethacrynic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D014129:Trabecular Meshwork / Q000187:drug effects* / Q000502:physiology
D004976:Ethacrynic Acid