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• W1985691820 abstract "Abstract With microsomes prepared from a single human liver, 4,4′-diaminodiphenyl sulphone (DDS), 4-acetyl-4-aminodiphenyl sulphone (MADDS), 4-acetyl-4-aminodiphenyl thioether (MADDT) and 4,4′-diacetyldiphenyl thioether (DADDT) caused significantly greater methaemoglobin formation compared with control. In-vitro in the rat, the pattern of toxicity was slightly different: DADDT was not haemotoxic, whilst 3,4′-diaminodiphenyl sulphone (3,4′DDS) and 3,3′-diaminodiphenyl sulphone (3,3′DDS) as well as DDS, MADDS and MADDT were significantly greater than control. 4,4′ Acetyl diphenyl sulphone (DADDS), 4,4′ diaminodiphenyl thioether (DDT), 4,4′-diaminodiphenyl ether (DDE) and 4,4′ diamino-octofluorodiphenyl sulphone (F8DDS) did not cause significant methaemoglobinaemia in either human or rat liver microsomes. DDS, MADDS, and MADDT were not significantly different in haemotoxicity generation in-vitro in the presence of human microsomes. In the rat in-vitro, DDS, MADDS, and 3,4′DDS did not differ significantly in red cell toxicity, and were the most potent methaemoglobin formers. The 3,3′ DDS and MADDT derivatives were both significantly less toxic compared with DDS. None of the compounds tested caused haemoglobin oxidation in the absence of NADPH in-vitro. In the whole rat, DDS, MADDS and MADDT caused significantly higher levels of methaemoglobin compared with control. None of the remaining compounds caused methaemoglobin formation which was significantly greater than control. DDS and MADDS were the most potent methaemoglobin formers tested, in-vivo and in-vitro. The 3,3′ and 3,4′DDS analogues caused no detectable haemotoxicity in-vivo. However, the plasma elimination of the 3,4′ analogue was much more rapid compared with that of DDS. Overall, there was no correlation between log k0 and increasing haemotoxicity. The use of the two-compartment system together with in-vivo studies may be applied to the evaluation of the structural features required for bioactivation of candidate antiparasitic compounds to haemotoxic metabolites by cytochrome P450 enzymes." @default.
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• W1985691820 date "1991-11-01" @default.
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• W1985691820 title "An Investigation into the Haematological Toxicity of Structural Analogues of Dapsone In-vivo and In-vitro" @default.
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• W1985691820 doi "https://doi.org/10.1111/j.2042-7158.1991.tb03481.x" @default.
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