RESUMO
The synthesis of a series of modularized porphyrins bearing bioactive molecule is described. Starting with meso-tetraphenylporphyrin, the compounds with two nitro functional groups were synthesized via regiospecific nitration reaction. After reduction to the amino group and subsequent coupling with l-phenylalanine or 1-carboxylmethyl-5-fluorouracil (5-Fu acid), the functionalized porphyrins were metallized with Co(II) or Mn(II) to form miscellaneous porphyrins in good yields. The spectra of all the porphyrins were furnished. In vitro photodynamic therapy of the porphyrins against Ec9706 cell line was evaluated by standard cytotoxicity assays.
Assuntos
Neoplasias Esofágicas/tratamento farmacológico , Compostos Organometálicos/síntese química , Compostos Organometálicos/farmacologia , Fenilalanina/química , Floroglucinol/análogos & derivados , Porfirinas/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cobalto/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Manganês/química , Estrutura Molecular , Compostos Organometálicos/efeitos da radiação , Floroglucinol/química , Floroglucinol/isolamento & purificação , Floroglucinol/farmacologia , Fotoquímica , Fotoquimioterapia , Estereoisomerismo , Relação Estrutura-Atividade , Raios UltravioletaRESUMO
Melanocyte-specific CD8(+) cytotoxic T lymphocytes (CTLs) play a pivotal role in vitiligo-induced depigmentation. Yet, the mechanisms underlying the high frequency of generalized autoimmune disorders associated with generalized vitiligo (GV) are unknown. We hypothesized that an imbalance between activated CD8(+) CTLs and regulatory T cells (Tregs) exists in patients with GV . Assessment of the circulating CD8(+) CTLs and Tregs by flow cytometric analysis revealed an obvious expansion of CD8(+) CTLs and a concomitant decrease in Treg cells in GV patients. The percentages of skin infiltrating CD8(+) CTLs and Tregs were evaluated by immunohistochemistry and revealed dramatically increased numbers of both CD8(+) CTLs and Tregs in the perilesional skin of GV patients. However, peripheral Tregs were impaired in their ability to suppress the proliferation and cytolytic capacity of autologous CD8(+) T cells, suggesting that a functional failure of Tregs and the hyper-activation of CD8(+) CTLs may contribute to progressive GV. Our data indicate that reduced numbers and impaired function of natural Tregs fail to control the widespread activation of CD8(+) CTLs, which leads to the destruction of melanocytes and contributes to the elevated frequency of various associated autoimmune diseases. This knowledge furthers our understanding of the mechanisms of immune tolerance that are impaired in GV patients and may aid in the future development of effective immunotherapy for GV patients.