Abstract
Microorganisms excrete low-molecular-weight ligands specific for iron (III) termed. “siderophore” for sequestering iron from the environment and transport it into a cell via the sophisticated iron transport system. More than 200 siderophores, which have been isolated and characterized, fall primarily into two structural classes; hydroxamic acid and catechol. Recently the author has report-ed on synthesis of hydroxyazine heterocycles, which are regarded as cyclic hydroxamic acids and/or catechol derivatives, and characterization of their iron (III) complexes. On the other hand, diabetes mellitus (DM), one of the most widespread disease in the world, is generally classified into insulin-depen-dent DM (IDDM) and non-insulin-dependent DM (NIDDM). Several chemotherapeutic agents for NIDDM have already been developed and clinically used. Patients with IDDM can be only treated by daily hypodemic injection of insulin, because it is easily degradated by the ingestive systems. Recently vanadyl complexes have received much attention because of their insulin-mimetic activities. In this review, the author would like to discuss 1) application of hydroxyazine heterocycles to chemotherapuetic agents for the iron-overload disease, 2) design of functional molecules containing hydroxamic acid, catechol, and hydroxyazine heterocyle, 3) application of siderophore-drug conjugates based upon the iron transport system to new antibiotics, and 4) the insulin-mimetic activity of heterocycle-VO (IV) complexes.
