肿瘤坏死因子(Tumor necrosis factor,TNF)是一类重要的细胞因子,可以调节发炎反应.TNF主要由受刺激的单核细胞、T细胞和细胞分裂素激活的B细胞分泌.适量的TNF-α能够激活患者的免疫系统,增强免疫力,但过量的TNF-α分泌往往造成其它组织的损伤.如果发现有效的抑制剂,来调节TNF-α生理活性的表达,则可以减轻或免除患者的痛苦,延长患者的生命.目前发现多肽是较好的抑制剂,但其体内半衰期极短,临床应用受到限制.后来又发展了类肽类抑制剂,其中具有二到三肽基本骨架的类肽化合物为有效的抑制剂(Scheme 1中1),这类抑制剂在体内易于弥散而不易降解,适合临床应用.
Tumor necrosis factor is one of the important cell factors, which can regulate pro-imflammatory. On the basis of the known and efficient peptidomimetic inhibitors of tumor necrosis factor as the leading compounds, novel sulfur-containing peptidomimetic inhibitors were designed and synthesized in a convenient and efficient manner. Bioassay results indicate that three of them showed some inhibition activity on sTNF-α secretion in HL-60 cells induced by lipolysaccharide, and two of them showed a good stability and inhibition activity.