Bis(maltolato)oxidovanadium(IV) ([VIVO(malt)2] or BMOV, where malt is maltolato) and bis(ethylmaltolato)oxidovanadium(IV) (BEOV) are among the most potent orally active insulin-mimetic agents. They have undergone extensive pre-clinical testing. Even though these experimentations were temporarily stopped due to renal problems of several patients and financial problems of Akesis Pharmaceuticals, BMOV is usually considered the reference for the new molecules with insulin-mimetic action. Surprisingly, recently the tests on BMOV are continued by CFM Pharma (CFM10, Vanadis) and now it is arrived to the phase II for the treatment of patients with injuries on secondary tissues caused by accidents or fire and with myocardial infarction. Proteins play a central role in the biospeciation of V compounds in the organism, because of both their high affinity toward V and their high concentration in biological fluids. Here, the interaction of BMOV with two model proteins has been analyzed by X-ray crystallography. Data indicate both non-covalent binding of cis-[VO(malt)2(H2O)] and [VO(malt)(H2O)3]+ and covalent binding of [VO(H2O)3-4]2+ and cis-[VO(malt)2] and other V-containing fragments to the side chains of Glu, Asp and to the C-terminal carboxylate. Thus, our results suggest a multiple and variable interaction of BMOV with proteins. Our data can help to better understand the BMOV solution chemistry and contribute to define the molecular basis of the mechanism of action of this intriguing metallodrug.
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Binding to proteins of the pharmacologically active bis(maltolato)oxidovanadium(IV)
Published: 01 November 2022 by MDPI in 8th International Electronic Conference on Medicinal Chemistry session Small molecules as drug candidates
https://doi.org/10.3390/ECMC2022-13266 (registering DOI)
Keywords: metallodrugs; protein metalation; V compounds; protein metal compounds interactions