Discovery of novel glitazones incorporated with phenylalanine and tyrosine: synthesis, antidiabetic activity and structure-activity relationships.
We report a series of new glitazones incorporated with phenylalanine and tyrosine. All the compounds were tested for their in vitro glucose uptake activity using rat-hemidiaphragm, both in presence and absence of insulin. Six of the most active compounds from the in vitro screening were taken forward for their in vivo triglyceride and glucose lowering activity against dexamethazone induced hyperlipidemia and insulin resistance in Wistar rats. The liver samples of rats that received the most active compounds, 23 and 24, in the in vivo studies, were subjected to histopathological examination to assess their short term hepatotoxicity. The investigations on the in vitro glucose uptake, in vivo triglyceride and glucose lowering activity are described here along with the quantitative structure-activity relationships.
Department of Pharmaceutical Chemistry, JSS College of Pharmacy, Mysore 570 015, India.
B R
BR
Prashantha Kumar
Nasir R
NR
Baig
Sai
S
Sudhir
Koyal
K
Kar
M
M
Kiranmai
M
M
Pankaj
Nanjan M
NM
Joghee
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006949:Hyperlipidemias / Q000139:chemically induced / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects / Q000473:pathology; D010649:Phenylalanine / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D045162:Thiazolidinediones / Q000138:chemical synthesis / Q000737:chemistry*; D014280:Triglycerides / Q000097:blood; D014443:Tyrosine / Q000737:chemistry*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D014280:Triglycerides; D014443:Tyrosine; D010649:Phenylalanine