Vanadyl complexes with insulin-mimetic activity

Abstracts

590

Kll

VANADYL COMPLEXES WITH INSULIN-MIMETIC ACTIVITY H. Sakurai, K. Fujii, H. Watanabe and H. Tamura Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Nakauchi-cho 5, Misasagi, Yamashina-ku, Kyoto 607, JAPAN The findings

that

v a n a d a t e (+5 oxidation

state

of vanadium)

is a potent

inhibitor of Na+, K+ -ATPase and thus has an i n s u l i n - m i m e t i c action stimulated research on bioinorganic chemistry. I n s u l i n - d e p e n d e n t diabetes mellitus (IDDM) due to absolute deficiency of insulin is controlled only by daily injections

of

insulin. The development of compounds that cause insulin

r e p l a c e m e n t s o r i n s u l i n - m i m e t i c s on o r a l a d m i n i s t r a t i o n would b e n e e d e d . On the basis of the fundamental study on v a n a d i u m - b i o i n o r g a n i c chemistry, we develope new insulin-mimetic vanadyl (+4 oxidation) complexes with various coordination modes that are less toxic than vanadate state. In evaluation of i n s u l i n - m i m e t i c action of the complex, we examine first the release of free fatty acid from the rat adipocytes and followed by in vivo test with streptozotocin-induced diabetic rats by intraperitoneal and oral administrations. In this paper we summarize the recent progress with vanadyl complexes [1, 2] as s h o w n b e l o w i n c l u d i n g t h o s e d e v e l o p e d b y o t h e r s (I, II, VIII, X and XII) a s w e l l as our newly synthesized complexes. [1] H. Watanabe et al., J. Med. Chem., 37, 876 (1994) [2] M. Nakai et al., Biol. Pharm. Bull, in press (1995) 1=12 RI

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