Inhibitory effect of pyridyloxy- or phenoxylphenoxyalkanate derivatives on rat lens aldose reductase and rat platelet aggregation.
The therapeutic potential of aldose reductase inhibitors for the prevention of the secondary complications of diabetes has been extensively reported. On the other hand, the hyperaggregability of platelets in diabetic patients has also been reported as a cause of chronic diabetic complications. The purpose of this study was to develop new compounds with these dual effects from pyridyloxy- or phenoxylphenoxyalkanate synthesized derivatives and examine the effect of their structure-activity relationships on the inhibition of rat lens aldose reductase (RLAR) as well as on platelet aggregation. 2-[4-(2,6-dichloro-3-methyl-phenoxy)-3-nitro-phenoxy]-propionic acid (3) exhibited the most potent inhibitory effect (IC(50) = 3.0 +/- 0.21 microM), comparable to tetramethylene glutaric acid (IC(50) = 6.1 +/- 0.2 microM), which is used as a positive control on RLAR, and showed potent inhibitory activities on rat platelet aggregation induced by ADP and collagen (IC(50) = 0.093 +/- 0.01 and 0.032 +/- 0.01 microM, respectively) comparable with aspirin (IC(50) = 0.15 +/- 0.05 and 0.047 +/- 0.01 microM, respectively), used as a positive control.
Lim
Soon Sung
SS
Silver Biotechnology Research Center, Hallym University, Chunchon 200-702, South Korea.
Shin
Kuk Hyun
KH
Jung
Sang Hoon
SH
Shin
Kye Jung
KJ
Kim
Dong Chan
DC
Park
Sang Woo
SW
Shin
Hyun Kyung
HK
Keum
Sam Rok
SR
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001555:Benzene Derivatives / Q000737:chemistry / Q000494:pharmacology*; D007908:Lens, Crystalline / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D011422:Propionates / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
D001555:Benzene Derivatives; D011422:Propionates; D011725:Pyridines; D000449:Aldehyde Reductase