An orally active antidiabetic vanadyl complex, bis(1-oxy-2-pyridinethiolato)oxovanadium(IV), with VO(S2O2) coordination mode; in vitro and in vivo evaluations in rats

Abstract According to Pearson’s HSAB (hard and soft acids and bases) rule, the vanadyl ion is classified as a hard acid. However, vanadyl–cysteine methyl ester and dithiocarbamate complexes with VO(S 2 N 2 ) and VO(S 4 ) coordination modes, respectively, that contain bonds with a combination of hard acid (VO 2+ ) and soft base (sulfur) have been found to form stable complexes and exhibit insulin-mimetic activities in in vitro and in vivo evaluations. Based on such observations, a purple bis(1-oxy-2-pyridinethiolato)oxovanadium(IV) (VO(OPT)) complex with VO(S 2 O 2 ) coordination mode was prepared and found to have a strong insulin-mimetic activity in in vitro evaluation, which followed in vivo effectiveness on intraperitoneal injection and oral administration. Then, we examined the real-time ESR analysis of vanadyl species in the blood of live rats given VO(OPT) by use of the blood circulation monitoring-ESR method. The clearance of vanadyl species from the blood in terms of half-life ( t 1/2 ) was determined as 15 min in VO(OPT)-treated rats, while t 1/2 of VOSO 4 -treated rats was 5 min, indicating the long-term acting character of VO(OPT). On the basis of the results, VO(OPT) with VO(S 2 O 2 ) coordination mode is proposed to be a potent orally active insulin-mimetic complex in treating insulin-dependent diabetes mellitus in experimental animals.