Al-Mulla Hummadi Yassir M, Al-Bashir Nada M, Najim Rafid A
Department of Pharmacology, College of Medicine, University of Baghdad, P.O. Box 61208, Baghdad 12114, Iraq.
Exp Parasitol. 2006 Feb;112(2):85-91. doi: 10.1016/j.exppara.2005.09.006. Epub 2005 Nov 7.
S(2) complex has been reported to have a direct antileishmanial effect. The possibility that the direct antileishmanial effect may be due to inhibition of key enzymes involved in glucose metabolism and/ or enzymes associated with virulence was investigated. Cell pellets were prepared from cultures of both axenic amastigotes and promastigotes of Leishmania major (MHOM/IQ/93/MRC6) and L. tropica (MHOM/IQ/93/MRC2). S(2) complex, at various concentrations, was added to the enzyme extracts prepared from the pellets. Results show that in the Embden-Meyerhof pathway, both hexokinase and glucose-phosphate isomerase but not fructophosphokinase were dose dependently inhibited. In the hexose-monophosphate shunt both glucose-6-phosphate dehydrogenase and ribose-5-phosphate isomerase were dose dependently inhibited. Malic dehydrogenase and malic enzyme from the citric-acid cycle were both dose dependently inhibited but succinate dehydrogenase from the same pathway was not inhibited. Both enzymes associated with virulence (protease and acid phosphatase), showed activation rather than inhibition at higher doses of S(2) complex. Thus, the direct antileishmanial effect of S(2) complex may result, partially or entirely, from the inhibition of enzymes that are necessary for the parasites' carbohydrate metabolism.
据报道，S(2)复合物具有直接抗利什曼原虫的作用。本研究调查了其直接抗利什曼原虫作用可能是由于抑制参与葡萄糖代谢的关键酶和/或与毒力相关的酶的可能性。从硕大利什曼原虫（MHOM/IQ/93/MRC6）和热带利什曼原虫（MHOM/IQ/93/MRC2）的无菌无鞭毛体和前鞭毛体培养物中制备细胞沉淀。将不同浓度的S(2)复合物添加到从沉淀中制备的酶提取物中。结果表明，在糖酵解途径中，己糖激酶和葡萄糖磷酸异构酶呈剂量依赖性抑制，而磷酸果糖激酶未受抑制。在磷酸戊糖途径中，6-磷酸葡萄糖脱氢酶和5-磷酸核糖异构酶均呈剂量依赖性抑制。柠檬酸循环中的苹果酸脱氢酶和苹果酸酶均呈剂量依赖性抑制，但同一途径中的琥珀酸脱氢酶未受抑制。两种与毒力相关的酶（蛋白酶和酸性磷酸酶）在高剂量S(2)复合物作用下表现为激活而非抑制。因此，S(2)复合物的直接抗利什曼原虫作用可能部分或完全源于对寄生虫碳水化合物代谢所必需的酶的抑制。
