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  • Title: Evaluation of anti-hyperglycemic activity of some novel monocyclic beta lactams.
    Author: Goel RK, Mahajan MP, Kulkarni SK.
    Journal: J Pharm Pharm Sci; 2004 Apr 21; 7(1):80-3. PubMed ID: 15144739.
    Abstract:
    PURPOSE: The present study was undertaken to examine the effect of monocyclic beta-lactams (compounds 5a-5o) for anti-hyperglycemic activity against alloxan-induced diabetes in rats. As these compounds have been shown to control disturbances in cholesterol metabolism induced by diabetes. METHODS: The test compounds were synthesized via [2+2] cycloaddition (Staudinger) reaction of imines with ketenes. The anti-hyperglycemic effect of test compounds was evaluated in alloxan-induced diabetes in rats by monitoring their effect on blood glucose and liver glycogen contents. RESULTS AND DISCUSSION: In the diabetic rats, high glucose levels and depression in hepatic glycogen contents were observed which could be attributed to the less availability of active form of enzyme glycogen synthetase. Test compounds significantly lowered the serum glucose levels indicating their anti-hyperglycemic activity. This activity of test compounds may be due to increased utilization of glucose as indicated by decreased serum glucose levels and an increase in the activity of glycogen synthetase enzyme as evidenced by rise in liver glycogen contents in test groups. Based on the results structure activity relationship (SAR) has been discussed and favorable substitutions around of monocyclic beta-lactam have been reported. Present study concluded that these compounds could have potential anti-hyperglycemic effect, which might be due to increased utilization of glucose either through increased insulin activity or induction of glycogen synthetase enzyme. CONCLUSION: Present study concluded that these compounds have significant anti-hyperglycemic effect. Further studies are required to reveal the mechanism of action.
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