Publications [#232440] of Emily R. Derbyshire

Journal Articles

1. Derbyshire, ER; Min, J; Guiguemde, WA; Clark, JA; Connelly, MC; Magalhães, AD; Guy, RK; Clardy, J, Dihydroquinazolinone inhibitors of proliferation of blood and liver stage malaria parasites., Antimicrobial agents and chemotherapy, vol. 58 no. 3 (January, 2014), pp. 1516-1522 [24366746], [doi]
   (last updated on 2024/12/31)

   Abstract:
   Drugs that target both the liver and blood stages of malaria will be needed to reduce the disease's substantial worldwide morbidity and mortality. Evaluation of a 259-member library of compounds that block proliferation of the blood stage of malaria revealed several scaffolds--dihydroquinazolinones, phenyldiazenylpyridines, piperazinyl methyl quinolones, and bis-benzimidazoles--with promising activity against the liver stage. Focused structure-activity studies on the dihydroquinazolinone scaffold revealed several molecules with excellent potency against both blood and liver stages. One promising early lead with dual activity is 2-(p-bromophenyl)-3-(2-(diethylamino)ethyl)-2,3-dihydroquinazolin-4(1H)-one with 50% effective concentrations (EC50s) of 0.46 μM and 0.34 μM against liver stage Plasmodium berghei ANKA and blood stage Plasmodium falciparum 3D7 parasites, respectively. Structure-activity relationships revealed that liver stage activity for this compound class requires a 3-dialkyl amino ethyl group and is abolished by substitution at the ortho-position of the phenyl moiety. These compounds have minimal toxicity to mammalian cells and are thus attractive compounds for further development.