PLASMODIUM-FALCIPARUM AND PLASMODIUM-BERGHEI - EFFECTS OF ORNITHINE DECARBOXYLASE INHIBITORS ON ERYTHROCYTIC SCHIZOGONY
PLASMODIUM-FALCIPARUM AND PLASMODIUM-BERGHEI - EFFECTS OF ORNITHINE DECARBOXYLASE INHIBITORS ON ERYTHROCYTIC SCHIZOGONY
复制标题
DOI：
10.1016/0014-4894(87)90148-2
复制
发表时间：
1987-10-01
影响因子：
2.1
通讯作者：
SJOERDSMA, A
中科院分区：
文献类型：
--
作者：
BITONTI, AJ;MCCANN, PP;SJOERDSMA, A
五种鸟氨酸脱羧酶抑制剂：-二氟甲基鸟氨酸（DFMO）（乙氟鸟氨酸）；.alpha.-monofluoromethyl-3 4-dehydroornithine;.alpha。-单氟甲基-3,4-脱氢鸟氨酸甲酯；.alpha。-单氟甲基-3,4-脱氢鸟氨酸乙酯；和(2R,5R)- δ -甲基- α -乙酰腐胺在体外抑制恶性疟原虫的红细胞分裂，并降低感染的甲状腺细胞中的亚精胺水平。在体内，只有DFMO能有效地限制伯氏假体红细胞分裂。在4天的抑制试验中，在饮用水中以2%的浓度给予DFMO 4天，使小鼠的寄生虫率降低了50%，但没有增加感染小鼠的生存时间。这是DFMO在体内对疟原虫红细胞分裂的作用的首次证明，并表明干扰多胺生物合成实际上可能是红细胞性疟疾的一个可行的化疗靶点。
Five ornithine decarboxylase inhibitors: .alpha.-difluoromethylornithine (DFMO) (eflornithine); .alpha.-monofluoromethyl-3,4-dehydroornithine; .alpha.-monofluoromethyl-3,4-dehydroornithine methyl ester; .alpha.-monofluoromethyl-3,4-dehydroornithine ethyl ester; and (2R,5R)-.delta.-methyl-.alpha.-acetylenic putrescine were shown to inhibit erythrocytic schizogony of Plasmodium falciparum in vitro and reduced spermidine levels in infected erthyrocytes. Only DFMO was effective at limiting erythrocyte schizogony of P. berghei in vivo. Administration of DFMO as a 2% solution in the drinking water for 4 days reduced parasitemia in mice by 50% in a 4-day suppression test but did not increase survival time of infected mice. This is the first demonstration of an effect of DFMO on plasmodial erythrocytic schizogony in vivo and suggests that interference with polyamine biosynthesis may, in fact, be a viable chemotherapeutic target in erythrocytic malaria.