CSIR Biosciences, Meiring Naude Road, Pretoria, 0001 Gauteng, South Africa.
Pharmacology Division, Department of Pharmacy and Pharmacology, WITS Research Institute for Malaria (WRIM), Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown 2193, South Africa.
Org Biomol Chem. 2016 Aug 16;14(33):7899-911. doi: 10.1039/c6ob01350c.
The design, synthesis and biological evaluation of a series of 6-aryl-1,6-dihydro-1,3,5-triazine-2,4-diamines is described. These compounds exhibited in vitro antiplasmodial activity in the low nanomolar range against both drug sensitive and drug resistant strains of P. falciparum, with 1-(3-(2,4-dichlorophenoxy)propyl)-6-phenyl-1,6-dihydro-1,3,5-triazine-2,4-diamine hydrochloride identified as the most potent compound from this series against the drug resistant FCR-3 strain (IC50 2.66 nM). The compounds were not toxic to mammalian cells at therapeutic concentrations and were shown to be inhibitors of parasitic DHFR in a biochemical enzyme assay.
描述了一系列 6-芳基-1,6-二氢-1,3,5-三嗪-2,4-二胺的设计、合成和生物评价。这些化合物在体外对敏感和耐药株疟原虫均表现出低纳摩尔范围的抗疟原虫活性，其中 1-(3-(2,4-二氯苯氧基)丙基)-6-苯基-1,6-二氢-1,3,5-三嗪-2,4-二胺盐酸盐对耐药 FCR-3 株的活性最强（IC50 为 2.66 nM）。这些化合物在治疗浓度下对哺乳动物细胞没有毒性，并在生化酶测定中被证明是寄生虫 DHFR 的抑制剂。
