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• W2001008027 abstract "It was previously noted that the inhibitory activities of lipophilic tetracyclines against the growth of Giardia lamblia in vitro were up to 40-fold greater than those of nonlipophilic tetracyclines (50% inhibitory concentration [IC50] = 1.8 to 71 micrograms/ml) (T. D. Edlind, Antimicrob. Agents Chemother. 33:2144-2145, 1989). We have now extended this observation to Trichomonas vaginalis (IC50 = 2.9 to 200 micrograms/ml), Entaoeba histolytica (IC50 = 3.8 to 36 micrograms/ml), and Leishmania major promastigotes (IC50 = 21 to 250 micrograms/ml; one strain only). The basis for these differential tetracycline activities was investigated with G. lamblia. In a cell-free protein synthesis system, lipophilic and nonlipophilic tetracyclines had similar, relatively low activities (IC50 = 170 to 500 micrograms/ml). On the other hand, tetracycline uptake into intact cells after a 1-h incubation varied dramatically: the ratios of intracellular to extracellular drug concentrations were 1.7 to 7.2 for nonlipophilic tetracyclines and 47 to 112 for lipophilic derivatives. Thus, the variable effects of tetracyclines on the growth of G. lamblia can be fully accounted for by differences in uptake. Passive diffusion probably plays a more important role than active transport in uptake of lipophilic tetracyclines, since similar results were obtained with cells rendered nonviable by metronidazole treatment." @default.
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• W2001008027 date "1991-11-01" @default.
• W2001008027 modified "2023-09-25" @default.
• W2001008027 title "Enhanced antiparasitic activity of lipophilic tetracyclines: role of uptake" @default.
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• W2001008027 doi "https://doi.org/10.1128/aac.35.11.2198" @default.
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