Influence of the Nucleobase on the Physicochemical Characteristics and Biological Activities of SbV-Ribonucleoside Complexes

نویسندگان

  • Cláudio S. Ferreira
  • Iara C. M. da Rocha
  • Rubens L. M. Neto
  • Maria N. Melo
  • Frédéric Frézard
  • Cynthia Demicheli
چکیده

A influência da nucleobase (uracila, U; citosina, C; adenina, A; guanina, G) nas propriedades físico-químicas e atividades biológicas in vitro dos complexos Sb-ribonucleosídeo foi investigada. Os complexos 1:1 Sb-U e Sb-C foram obtidos no estado sólido e caracterizados por RMN, ESI-MS e análise elementar. As constantes de estabilidade e as constantes aparentes de velocidade de formação e dissociação dos complexos 1:1 Sb-U, Sb-C e Sb-A foram determinadas. Embora o Sb se ligue através dos mesmos átomos de oxigênio das posições 2' e 3' nos diferentes nucleosídeos, as mudanças conformacionais na ribose e as propriedades físico-químicas do complexo dependem da nucleobase. A nucleobase influenciou fortemente as atividades citotóxica e leishmanicida dos complexos Sb-ribonucleosídeo. Os complexos Sb-nucleosídeos purínicos foram mais citotóxicos e eficazes contra a Leishmania chagasi do que os pirimidínicos, o que reforça o modelo de que a interação do Sb com os nucleosídeos purínicos pode mediar a atividade dos medicamentos antimoniais.

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تاریخ انتشار 2010