Pharmacological and Pharmacokinetic Studies of Anti-diabetic Tropolonato-Zn(II) Complexes with Zn(S(2)O(2)) Coordination Mode
News Sep 17, 2012
Zn(II) complexes are expected to be useful in the treatment of diabetes mellitus because of the hypoglycemic effect produced by its insulin-mimetic activity. Previous reports indicated that Zn(II) complexes with coordinating sulfur exhibit higher insulin-mimetic activity. In this study, we investigated the pharmacological and pharmacokinetic differences between Zn(O(4)) and Zn(S(2)O(2)) coordination modes of tropolonato-Zn(II) complexes with insulin-mimetic activity. Among the tropolonato-Zn(II) complexes with various coordination modes, di(2-mercaptotropolonato)zinc(II) (ZT2) with the Zn(S(2)O(2)) coordination mode was found to exhibit the highest in vitro insulin-mimetic activity with respect to inhibition of free fatty acid (FFA) release and enhancement of glucose uptake in isolated rat adipocytes treated with adrenaline. On comparing investigations of the antidiabetic effect in vivo, ZT2 was found to exhibit potent hypoglycemic activity and improve insulin resistance in type 2 diabetic KKA(y) mice at a low orally administered daily dose. Di(tropolonato)zinc(II) (ZT1), which has the Zn(O(4)) coordination mode, had a lesser effect at the same dose. In a pharmacokinetic analysis based on the (65)Zn tracer method, ZT2 was found to be absorbed at a significantly slower rate with a longer half-life than was ZT1. These results suggest that the potent hypoglycemic activity of ZT2 might be attributed to its long half-life.
The article is published online in Chemical and Pharmaceutical Bulletin and is free to access.
Research Team Discovers Compound that Stops Cancer From SpreadingNews
Using a mouse model, OHSU physician-scientists lead effort to hone a drug that inhibits cancer cells from spreading to other areas in the body.READ MORE
PhoreMost and o2h Discovery Collaborate to Progress First-in-Class Drug Discovery ProgramsNews
PhoreMost, the UK-based biopharmaceutical company dedicated to drugging ‘undruggable’ disease targets, announced it has entered into a collaboration with o2h discovery (o2h), an Anglo-Indian medicinal chemistry company that has in-house capability to take drug discovery programmes to the IND filing stage.READ MORE
Compound as Effective as FDA-Approved Drugs Against Life-Threatening InfectionsNews
Purdue University researchers have identified a new compound that in preliminary testing has shown itself to be as effective as antibiotics approved by the Food and Drug Administration to treat life-threatening infections while also appearing to be less susceptible to bacterial resistance.READ MORE