一种具有强效、靶向和选择性抗疟原虫活性的泛硫乙胺酶抗性泛酰乙胺。
A pantetheinase-resistant pantothenamide with potent, on-target, and selective antiplasmodial activity.
作者信息
Macuamule Cristiano J, Tjhin Erick T, Jana Collins E, Barnard Leanne, Koekemoer Lizbé, de Villiers Marianne, Saliba Kevin J, Strauss Erick
机构信息
Department of Biochemistry, Stellenbosch University, Stellenbosch, South Africa.
Research School of Biology, College of Medicine, Biology, and Environment, The Australian National University, Canberra, ACT, Australia.
出版信息
Antimicrob Agents Chemother. 2015;59(6):3666-8. doi: 10.1128/AAC.04970-14. Epub 2015 Apr 6.
Abstract
Pantothenamides inhibit blood-stage Plasmodium falciparum with potencies (50% inhibitory concentration [IC50], ∼20 nM) similar to that of chloroquine. They target processes dependent on pantothenate, a precursor of the essential metabolic cofactor coenzyme A. However, their antiplasmodial activity is reduced due to degradation by serum pantetheinase. Minor modification of the pantothenamide structure led to the identification of α-methyl-N-phenethyl-pantothenamide, a pantothenamide resistant to degradation, with excellent antiplasmodial activity (IC50, 52 ± 6 nM), target specificity, and low toxicity.
摘要
泛硫乙胺抑制恶性疟原虫血液期的效力（50%抑制浓度[IC50]，约20 nM）与氯喹相似。它们作用于依赖泛酸盐（必需代谢辅因子辅酶A的前体）的过程。然而，由于血清泛肽酶的降解作用，它们的抗疟原虫活性降低。对泛硫乙胺结构进行微小修饰后，鉴定出α-甲基-N-苯乙基-泛硫乙胺，这是一种抗降解的泛硫乙胺，具有出色的抗疟原虫活性（IC50，52±6 nM）、靶标特异性和低毒性。
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