کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1317137 976509 2007 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Naturally occurring cobalamins have antimalarial activity
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی معدنی
پیش نمایش صفحه اول مقاله
Naturally occurring cobalamins have antimalarial activity
چکیده انگلیسی

The acquisition of resistance by malaria parasites towards existing antimalarials has necessitated the development of new chemotherapeutic agents. The effect of vitamin B12 derivatives on the formation of β-haematin (synthetic haemozoin) was determined under conditions similar to those in the parasitic food vacuole (using chloroquine, a known inhibitor of haemozoin formation for comparison). Adenosylcobalamin (Ado-cbl), methylcobalamin (CH3-cbl) and aquocobalamin (H2O-cbl) were approximately forty times more effective inhibitors of β-haematin formation than chloroquine, cyanocobalamin (CN-cbl) was slightly more inhibitory than chloroquine, while dicyanocobinamide had no effect. It is proposed that the cobalamins exert their inhibitory effect on β-haematin formation by π-interactions of their corrin ring with the Fe(III)-protoporphyrin ring and by hydrogen-bonding using their 5,6-dimethylbenzimidazole/ribose/sugar side-chain. The antimalarial activity for the cobalamins (Ado-cbl > CH3-cbl > H2O-cbl > CN-cbl) was found to be less than that for chloroquine or quinine. Ado-cbl, CH3-cbl and CN-cbl do not accumulate in the parasite food vacuole by pH trapping, but H2O-cbl does. Unlike humans, the malaria parasite has only one enzyme that uses cobalamin as a cofactor, namely methionine synthase, which is important for growth and metabolism. Thus cobalamins in very small amounts are necessary for Plasmodium falciparum growth but in larger amounts they display antimalarial properties.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Inorganic Biochemistry - Volume 101, Issue 5, May 2007, Pages 764–773
نویسندگان
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