Synthesis and characterization of dual function vanadyl, gallium and indium curcumin complexes for medicinal applications.

Novel bis[4-hydroxy-3-methoxyphenyl]-1,6-heptadiene-3,5-dione (curcumin) complexes with the formula, ML(3), where M is Ga(III) or In(III), or of the formula, ML(2) where M is [VO](2+), have been synthesized and characterized by mass spectrometry, infrared and absorption spectroscopies, and elemental analysis. A new ligand, bis[4-acetyl-3-hydroxyphenyl]-1,6-heptadiene-3,5-dione (diacetylbisdemethoxycurcumin, DABC) was similarly characterized; an X-ray structure analysis was performed. Vanadyl complexes tested in an acute i.p. testing protocol in STZ-diabetic rats showed a lack of insulin enhancing potential. Vanadyl complexes were, however, more cytotoxic than were the ligands alone in standard MTT (3-[4,5-dimethylthiazole-2-yl]ate, -2,5-diphenyl-tetrazolium bromide) cytotoxicity testing, using mouse lymphoma cells. With the exception of DABC, that was not different from VO(DABC)(2), the complexes were not significantly different from one another, with IC(50) values in the 5-10 microM range. Gallium and indium curcumin complexes had IC(50) values in the same 5-10 microM range; whereas Ga(DAC)(3) and In(DAC)(3) (where DAC=diacetylcurcumin) were much less cytotoxic (IC(50)=20-30 microM). Antioxidant capacity was decreased in VO(DAC)(2), Ga(DAC)(3), and In(DAC)(3), compared to vanadyl, gallium and indium curcumin, corroborating the importance of curcumin's free phenolic OH groups for scavenging oxidants, and correlated with reduced cytotoxic potential.