Novel vanadyl complexes with quinoxaline N, N'-dioxide derivatives bearing in vitro biological activity

DINORAH GAMBINO; CAROLINA URQUIOLA1; PABLA NOBLÍA; MARISOL VIEITES1; MARÍA H. TORRE1; HUGO CERECETTO; MARÍA LAVAGGI; GABRIELA AGUIRRE; MERCEDES GONZÁLEZ; ANTONIO COSTA-FILHO; AMAIA AZQUETA; ADELA LÓPEZ; ANTONIO MONGE; BEATRIZ PARAJÓN-COSTA

San Francisco

Simposio; 5th International Symposium on Chemistry and Biological Chemistry of Vanadium como parte del 232nd American Chemical Society National Meeting; 2006

Seven vanadyl complexes VO(L)2, where L are bidentate aminoquinoxaline carbonitrile N,N´-dioxides have been synthesized as an effort to develop novel metal-based selective hypoxia-cytotoxins and/or anti-Trypanosoma cruzi agents by improving the bioactivity of the free ligands. Complexes were characterized by elemental analyses, conductometry, FAB-MS and electronic, FTIR, Raman and EPR spectroscopies. Electrochemical behavior of the free ligands and the complexes has been studied. Tested complexes resulted in vitro (V79 cells) more potent cytotoxins than the free ligands and Tirapazamine and showed excellent selective cytotoxicity in hypoxia, being no cytotoxic in oxia. In addition, complexation of the quinoxaline ligands lead to excellent antiprotozoal activity, similar to that of the reference drugs Nifurtimox and Benznidazol and in all cases higher than that of the corresponding free ligands. Structure-activity relationship studies allowed to explain the anti-trypanosomal activity of these vanadium complexes on the basis of lipophilicity and electronic characteristics of the quinoxaline substituents.