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• W2950961639 endingPage "224" @default.
• W2950961639 startingPage "215" @default.
• W2950961639 abstract "Abstract Previous work from our laboratory shows that compounds with two cations linked by a carbazole spacer were highly potent antiP. carinii agents. A prodrug approach designed to increase oral activity of the dicationic carbazoles by converting amidine groups to amidoxime groups was unsuccessful. The ring nitrogen was implicated as playing a role in the lack of activity of carbazole amidoximes. The current study was designed to determine if replacement of the carbazole ring nitrogen by isosteric oxygen to form dibenzofurans would improve effectiveness of amidoxime prodrugs. Eight dibenzofuran dicationic derivatives were synthesized and evaluated for anti-P. carinii activity in an immunosuppressed rat model. Since DNA binding has been hypothesized to play a key role in antimicrobial activity of dicationic compounds, the compounds were examined for their binding affinity to calf thymus DNA and a poly-dA•poly-dT oligomer. While several of the compounds were more potent anti-P. carinii agents than pentamidine, the corresponding amidoximes were significantly less effective than the amidoxime of pentamidine. No direct quantitative correlation was determined between DNA binding affinity and anti-P. carinii activity, but all active compounds were strong DNA binding agents." @default.
• W2950961639 created "2019-06-27" @default.
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• W2950961639 date "1999-03-01" @default.
• W2950961639 modified "2023-10-18" @default.
• W2950961639 title "Dicationic dibenzofuran derivatives as anti-Pneumocystis carinii pneumonia agents: synthesis, DNA binding affinity, and anti-P. carinii activity in an immunosuppressed rat model" @default.
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• W2950961639 doi "https://doi.org/10.1016/s0223-5234(99)80054-3" @default.
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