通过DNA聚合酶α全酶的自杀失活实现低毒性癌症化疗：新型噻唑烷基和全氢噻嗪基乙基氮芥磷酰胺酯的初步结果
Low toxicity cancer chemotherapy by suicide inactivation of DNA polymerase alpha holoenzyme: first results with new thiazolidinyl- and perhydrothiazinyl-ethyl-N-mustard-phosphamide esters.
作者信息
Hohorst H J, Bielicki L, Müller K, Voelcker G
机构信息
Gustav-Embden-Zentrum of Biological Chemistry, University of Frankfurt/Main, Federal Republic of Germany.
出版信息
J Cancer Res Clin Oncol. 1988;114(3):309-11. doi: 10.1007/BF00405840.
Abstract
Thiazolidinyl- and perhydrothiazinyl-ethyl-N-mustard-phosphamide esters were designed to act as highly specific suicide inactivators of DNA polymerase alpha holoenzymes. Acute and subacute toxicity of these drugs in mice was very small. By daily i.p. injection, on day 0-4 mice were cured of P 388 lymphatic leukaemia with no depression of blood leucocytes. The findings suggest that suicide inactivators of DNA polymerase alpha holoenzyme may be promising drugs for low toxicity cancer chemotherapy.
摘要
噻唑烷基和全氢噻嗪基乙基-N-芥子气磷酰胺酯被设计用作DNA聚合酶α全酶的高度特异性自杀性灭活剂。这些药物对小鼠的急性和亚急性毒性非常小。通过每日腹腔注射，在第0至4天，P 388淋巴细胞白血病小鼠被治愈，且血液白细胞未出现减少。这些发现表明，DNA聚合酶α全酶的自杀性灭活剂可能是低毒性癌症化疗的有前景的药物。
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