Naylor M A, Stephens M A, Cole S, Threadgill M D, Stratford I J, O'Neill P, Fielden E M, Adams G E
Medical Research Council Radiobiology Unit, Didcot, Oxon, UK.
J Med Chem. 1990 Sep;33(9):2508-13. doi: 10.1021/jm00171a027.
A series of 5-nitrofuran-2- and 3-carboxamides bearing alkylating side-chains has been synthesized and tested for their ability to radiosensitize selectively hypoxic Chinese hamster cells (V79) to the lethal effects of ionizing radiation and also for their ability to act directly and selectively as cytotoxic drugs on hypoxic V79 cells. The compounds were extremely efficient radiosensitizers of such cells in vitro and were more efficient than known nitroimidazoles of similar type. Their efficiencies as radiosensitizers correlated with their high electron affinity (E7(1] as measured by pulse-radiolysis. However the compounds showed little radiosensitizing activity towards KHT sarcomas in C3H mice. The compounds in this series of nitrofurans were generally more toxic towards hypoxic cells than towards oxic cells in vitro but were less effective upon the basis of a differential effect than were similar nitroimidazoles reported previously.
已合成了一系列带有烷基化侧链的5-硝基呋喃-2-羧酰胺和5-硝基呋喃-3-羧酰胺，并测试了它们选择性地使缺氧的中国仓鼠细胞（V79）对电离辐射的致死效应产生放射增敏的能力，以及它们直接并选择性地作为细胞毒性药物作用于缺氧V79细胞的能力。这些化合物在体外是此类细胞极其有效的放射增敏剂，并且比类似类型的已知硝基咪唑更有效。它们作为放射增敏剂的效率与它们通过脉冲辐射分解测量的高电子亲和力（E7）相关。然而，这些化合物对C3H小鼠的KHT肉瘤几乎没有放射增敏活性。这一系列硝基呋喃化合物在体外通常对缺氧细胞的毒性比对有氧细胞的毒性更大，但基于差异效应，其效果不如先前报道的类似硝基咪唑有效。
