One-pot, multicomponent synthesis of 2,3-disubstituted quinazolin-ones with potent and selective activity against Toxoplasma gondii.
The discovery of two quinazolinones with selective, single-digit micromolar activity (IC50 = 6-7 µM) against the tachyzoites of the apicomplexan parasite Toxoplasma gondii is reported. These potent and selective third generation derivatives contain a benzyloxybenzyl substituent at C2 and a bulky aliphatic moiety at N3. Here we show that these quinazolinones inhibit T. gondii tachyzoite replication in an established infection, but do not significantly affect host cell invasion by the tachyzoites.
['Brown|Carla E|CE|', 'Kong|Tiffany|T|', 'Bordón|Claudia|C|', 'Yolken|Robert|R|', 'Jones-Brando|Lorraine|L|', 'McNulty|James|J|']
D000981:Antiprotozoal Agents D049109:Cell Proliferation D004305:Dose-Response Relationship, Drug D005347:Fibroblasts D006801:Humans D015394:Molecular Structure D021261:Parasitic Sensitivity Tests D052999:Quinazolinones D012867:Skin D013329:Structure-Activity Relationship D014122:Toxoplasma
Toxoplasma gondii Quinazolinone Multi-component synthesis Toxoplasmosis