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α-酮醛,包括甲基乙二醛的抗癌作用已有过报道,然而,这些药物由于乙二醛酶(Glyoxalase)的作用迅速被代谢成为无活性的α-羟基酸。该发现提示,选择一个适当的乙二醛酶抑制剂并与α-酮醛合并用药可能是化学治疗的一种有效方法。已知S-取代的谷胱甘肽衍生物对从酵母中提得的乙二醛酶(Ⅰ)为一有效的抑制剂,其中有些衍生物对L-1210白血病和组织培养的KB细胞显示细胞毒性,同时增加甲基乙二醛对L-1210细胞的毒性。但是S-取代谷胱甘肽衍生物在小鼠体内被谷胱甘肽酶迅速代谢,使得这类抑制剂在体内试验时失效。
The anticancer effects of alpha-ketoaldehydes, including methylglyoxal, have been reported, however, these drugs are rapidly metabolized as inactive alpha-hydroxy acids due to the action of glyoxalase. This finding suggests that selecting an appropriate glyoxalase inhibitor and combining it with alpha-ketoaldehyde may be an effective method of chemotherapy. S-substituted glutathione derivatives are known to be potent inhibitors of glyoxalase (I) derived from yeast, some of which exhibit cytotoxicity to L-1210 leukemia and tissue culture KB cells showing cells Toxicity, while increasing the toxicity of methylglyoxal to L-1210 cells. However, S-substituted glutathione derivatives are rapidly metabolized by glutathione in mice, rendering such inhibitors ineffective in vivo.