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  • Title: Fluorinated analogues of L-ornithine are powerful inhibitors of ornithine decarboxylase and cell growth of Leishmania infantum promastigotes.
    Author: Reguera RM, Fouce RB, Cubría JC, Bujidos ML, Ordóñez D.
    Journal: Life Sci; 1995; 56(4):223-30. PubMed ID: 7823781.
    Abstract:
    Fluorinated analogues of L-ornithine have been tested on growth and ornithine decarboxylase arising from L.infantum cytosolic extracts. EC50 values estimated from dose/response curves were 38 microM, 2.62 microM and 4.64 microM for alpha-DFMO, delta-MFMO and delta-MFMOme respectively. Also the inhibition produced by all three compounds was effectively reverted by exogenous putrescine, pointing towards the inhibition of L.infantum ODC. ODC from logarithmic phase cytosolic extracts was physicochemically and kinetically characterized, showing a long half-life (more than 24 h) and a km value for L-ornithine of 98 microM. Finally, the inhibitory effect of fluorinated analogues of L-ornithine was analysed on L.infantum ODC showing a time-dependent irreversible behavior, with Ki values estimated on 125 microM, T1/2 3.5 min for alpha-DFMO; 13.3 microM, T1/2 1.8 min for delta-MFMO and 4.3 microM, T1/2 4 min for delta-MFMOme.
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