Synthesis of Arylpiperazines as Perspective Toxoplasma gondii Dihydrofolate Reductase Inhibitors
Toxoplasmosis is a parasitic disease caused by Toxoplasma gondii. Approximately one-third of the population worldwide is chronically infected with T. gondii. First-line treatment of toxoplasmosis is a therapy based on dihydrofolate reductase (DHFR, DHFRP1, DYR) inhibitors which act on the folate metabolic pathway, thereby inhibiting T. gondii proliferation and survival.
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A recent paper from the Journal of Medicinal Chemistry* showed that authors synthesized a series of arylpiperazines through structural modification of TRC-19 (a lead compound from their previous study, IC50 = 8.76 nM). Among them, compound 3 (5-(4-(3-(2-methoxypyrimidin-5-yl)phenyl)piperazin-1-yl)pyrimidine-2,4-diamine) showed activity against dihydrofolate reductase of T. gondii (IC50 = 1.57 nM) and good selectivity ratio between Human DHFR and Toxoplasma DHFR