Synthesis of metal complexes with 1-substituted 3-hydroxy-2(1H)-pyridinethiones and their insulin-mimetic activities

Eight kinds of 1-alkyl-3-hydroxy-2(1H-pyridinethiones were synthesized from a commercially available 3-methoxy-2(1H)-pyridinone via 3 steps. Zn(II) and vanadyl complexes were synthesized by treatment with Zn(OAC) 2 or ZnS0 4 , and VOS0 4 , respectively. Vanadyl complexes were found to exist in VO(S 2 O 2 ) coordination mode by means of ESR spectroscopy. From in vitro evaluation of the inhibitory effect on FFA release from rat adipocytes treated with epinephrine, it was found that IC 50 values of Zn(II) complexes with 1-alkyl-3-hydroxy-2(1H)-pyridinethiones, regardless of the methylene-chain length at N-1 position, were in micromolar levels. In other words, these Zn(II) complexes showed higher insulin-mimetic activities than those synthesized previously. On the other hand, the insulin-mimetic activity of vanadyl complexes unfortunately could not be measured owing to their insolubility in KRB buffer which is used in vitro assay.