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, ML3, where M is Ga(III) or In(III), or of the formula, ML2 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 IC50 values in the 5-10 mu M range. Gallium and indium curcumin complexes had IC50 values in the same 5-10 mu M range; whereas Ga(DAC)(3) and In(DAC)(3) (where DAC = diacetylcurcumin) were much less cytotoxiC (IC50 = 20-30 mu M). 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. (c) 2005 Elsevier Inc. All rights reserved.