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• W2466291228 abstract "We tested a series of amidine and related compounds against Trypanosoma brucei. The most active compound was a biphenyldiamidine that had an EC50 of 7.7 nM against bloodstream-form parasites. There was little toxicity against two human cell lines with CC50 > 100 μM. There was also good in vivo activity in a mouse model of infection with 100% survival at 3 mg/kg i.p. The most potent lead blocked replication of kinetoplast DNA (k-DNA), but not nuclear DNA, in the parasite. Some compounds also inhibited the enzyme farnesyl diphosphate synthase (FPPS), and some were uncouplers of oxidative phosphorylation. We developed a computational model for T. brucei cell growth inhibition (R2 = 0.76) using DNA ΔTm values for inhibitor binding combined with T. brucei FPPS IC50 values. Overall, the results suggest that it may be possible to develop multitarget drug leads against T. brucei that act by inhibiting both k-DNA replication and isoprenoid biosynthesis." @default.
• W2466291228 created "2016-07-22" @default.
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• W2466291228 date "2015-07-31" @default.
• W2466291228 modified "2023-10-15" @default.
• W2466291228 title "In Vitro and in Vivo Activity of Multitarget Inhibitors against <i>Trypanosoma brucei</i>" @default.
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• W2466291228 doi "https://doi.org/10.1021/acsinfecdis.5b00068" @default.
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• W2466291228 hasPublicationYear "2015" @default.
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