Influence of the nucleobase on the physicochemical characteristics and biological activities of SbV-ribonucleoside complexes

Journal of the Brazilian Chemical Society

Universidade Federal de Minas Gerais, Belo Horizonte, Brazil¹  Ferreira, Cláudio S.¹  Frézard, Frédéric¹  Rocha, Iara C. M. da¹  M. Neto, Rubens L.¹  Demicheli, Cynthia¹  Melo, Maria N.¹ 

关键词: antimony;    kinetics;    nucleosides;    cytotoxicity;    leishmaniasis;   

DOI  :  10.1590/S0103-50532010000700013

学科分类：化学（综合）

来源: SciELO

【 摘 要 】

The influence of the nucleobase (uracyl, U; cytosine, C; adenine, A; guanine, G) on the physicochemical characteristics and in vitro biological activities of SbV-ribonucleoside complexes has been investigated. The 1:1 Sb-U and Sb-C complexes were characterized by NMR and ESI-MS spectroscopies and elemental analysis. The stability constant and the apparent association and dissociation rate constants of 1:1 SbV-U, SbV-C and SbV-A complexes were determined. Although SbV most probably binds via oxygen atoms to the same 2' and 3' positions in the different nucleosides, the ribose conformational changes and the physicochemical characteristics of the complex depend on the nucleobase. The nucleobase had a strong influence on the cytotoxicity against macrophages and the antileishmanial activity of the SbV-ribonucleoside complexes. The SbV-purine complexes were more cytotoxic and more effective against Leishmania chagasi than the SbV-pyrimidine complexes, supporting the model that the interaction of SbV with purine nucleosides may mediate the antileishmanial activity of pentavalent antimonial drugs.

【 授权许可】

Unknown