One-pot, multicomponent synthesis of 2, 3-disubstituted quinazolin-ones with potent and selective activity against Toxoplasma gondii. Issue 9 (15th May 2018)

• Record Type: Journal Article
• Authors: Brown, Carla E.; Kong, Tiffany; Bordón, Claudia; Yolken, Robert; Jones-Brando, Lorraine; McNulty, James
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 9(2018)
• Page Start: 1642
• Page End: 1646
• Publication Date: 2018-05-15
• Subjects: Toxoplasmosis -- Toxoplasma gondii -- Quinazolinone -- Multi-component synthesis; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2018.03.036
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: 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 C 2 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.