{'fraction_non_alphanumeric': 0.034045008655510675, 'fraction_numerical': 0.006924408540103866, 'mean_word_length': 5.826771653543307, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 1, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
[Development research of new Zn complexes with anti-diabetic effect--structure-activity-related studies by displacement of coordination atom].

The number of patients suffering from diabetes mellitus in 2007 was reported to be approximately 200 million people worldwide. Since the finding of insulinomimetic activity of Zn ion, several insulinomimetic Zn complexes have been reported. Zn complexes are expected to be useful in the treatment of diabetes mellitus. We reported that Zn complexes with coordinating sulfur atom exhibit higher insulin-mimetic activity. In this study, we investigated the pharmacological and pharmacokinetic differences between Zn(O₄) and Zn(S₂O₂) coordination environments of tropolonate-Zn complexes with antidiabetic effect. Among the tropolonate-Zn complexes with various coordination environments, di(2-mercaptotropolonato)Zn with the Zn(S₂O₂) coordination environments was found to exhibit the highest in vitro insulinomimetic activity with respect to glucose uptake in isolated rat adipocytes treated with adrenaline. In vivo experiments, di(2-mercaptotropolonato)Zn 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. On the other hand, di(tropolonato)Zn, which has the Zn(O₄) coordination mode, had a lesser effect at the same dose. In a pharmacokinetic analysis based on the tracer method, di(2-mercaptotropolonato)Zn was found to be absorbed at a significantly slower rate with a longer half-life than di(tropolonato)Zn. These results suggest that the potent hypoglycemic activity of di(2-mercaptotropolonato)Zn with Zn(S₂O₂) coordination environments might be attributed to its long half-life.