Bitonti A J, Baumann R J, Jarvi E T, McCarthy J R, McCann P P
Merrell Dow Research Institute, Cincinnati, OH 45215.
Biochem Pharmacol. 1990 Aug 1;40(3):601-6. doi: 10.1016/0006-2952(90)90562-y.
A 4',5'-unsaturated 5'-fluoroadenosine inhibitor of S-adenosyl-L-homocysteine hydrolase (SAH hydrolase; EC 3.3.1.1), MDL 28842, was found to inhibit markedly the growth of Plasmodium falciparum in vitro and Plasmodium berghei in mice. Inhibition of P. berghei growth was associated with a large increase in the concentration of S-adenosyl-L-homocysteine (SAH) in the erythrocytes of the mice treated with MDL 28842. This increase in SAH was due apparently to inhibition of the mouse erythrocyte SAH hydrolase activity, because SAH hydrolase activity was undetectable in either P. berghei or P. falciparum isolated from infected erythrocytes, although enzyme activity was readily detected in mouse erythrocyte extracts. Therefore, MDL 28842 probably inhibits plasmodial growth indirectly by adversely changing the milieu of the host erythrocyte. SAH hydrolase represents a worthwhile target for the future development of potent inhibitors for the chemotherapy of malaria.
S-腺苷-L-高半胱氨酸水解酶（SAH水解酶；EC 3.3.1.1）的一种4',5'-不饱和5'-氟腺苷抑制剂MDL 28842，被发现能显著抑制恶性疟原虫在体外的生长以及伯氏疟原虫在小鼠体内的生长。对伯氏疟原虫生长的抑制与用MDL 28842处理的小鼠红细胞中S-腺苷-L-高半胱氨酸（SAH）浓度的大幅增加有关。SAH的这种增加显然是由于小鼠红细胞SAH水解酶活性受到抑制，因为从感染红细胞中分离出的伯氏疟原虫或恶性疟原虫中均未检测到SAH水解酶活性，尽管在小鼠红细胞提取物中很容易检测到酶活性。因此，MDL 28842可能通过不利地改变宿主红细胞的环境间接抑制疟原虫的生长。SAH水解酶是未来开发用于疟疾化疗的有效抑制剂的一个有价值的靶点。
