warfarin and cyclocumarol

warfarin has been researched along with cyclocumarol* in 3 studies

Other Studies

3 other study(ies) available for warfarin and cyclocumarol

ArticleYear
Structural forms of phenprocoumon and warfarin that are metabolized at the active site of CYP2C9.
    Archives of biochemistry and biophysics, 1999, Dec-01, Volume: 372, Issue:1

    Possible reasons for the observed differences in metabolic behavior and drug interaction liability between the structurally similar oral anticoagulants warfarin and phenprocoumon were explored. Incubating (S)-phenprocoumon with human liver microsomes and cDNA-expressed CYP2C9 and determining its metabolism both in the absence and presence of the CYP2C9 inhibitor, sulfaphenazole, confirmed that phenprocoumon is a substrate for CYP2C9. Comparing the metabolic behavior of (S)- and (R)-warfarin, (S)- and (R)-phenprocoumon, and fixed structural mimics of the various tautomeric forms [(S)- and (R)-4-methoxyphenprocoumon, (S)- and (R)-2-methoxyphenprocoumon, (S)- and (R)-4-methoxywarfarin, (S)- and (R)-2-methoxywarfarin, and 9(S)- and 9(R)-cyclocoumarol] available to these two drugs with expressed CYP2C9 provides compelling evidence indicating that the ring closed form of (S)-warfarin and the ring opened anionic form of (S)-phenprocoumon are the major and specific structural forms of the two drugs that interact with the active site of CYP2C9. The conclusion that (S)-warfarin and (S)-phenprocoumon interact with CYP2C9 in very different structural states provides a clear basis for the significant differences observed in their metabolic profiles. Moreover, in accord with a previously established CoMFA model these results are consistent with the hypothesis that the active site of CYP2C9 possesses at least two major substrate binding sites, a pi-stacking site for aromatic rings and an ionic binding site for organic anions. An additional electrostatic binding site also appears to contribute to the orientation of coumarin analogs in the CYP2C9 active site by interacting with the C2-carbonyl group of the coumarin nucleus.

    Topics: 4-Hydroxycoumarins; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Catalytic Domain; Cytochrome P-450 CYP2C9; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Drug Interactions; Humans; In Vitro Techniques; Kinetics; Microsomes, Liver; Models, Molecular; Phenprocoumon; Recombinant Proteins; Stereoisomerism; Steroid 16-alpha-Hydroxylase; Steroid Hydroxylases; Substrate Specificity; Sulfaphenazole; Warfarin

1999
Inhibitory effect of coumarins on HIV-1 replication and cell-mediated or cell-free viral transmission.
    Acta virologica, 1993, Volume: 37, Issue:4

    A single dose of coumarin derivatives, warfarin, 4-hydroxycoumarin and umbelliferone, added at the time of inoculation either by free virus or by contact with U1 monocytes exhibited a dose-dependent inhibitory effect on viral replication in target MOLT-4 lymphocytes observable even at 5 days post infection. In addition, marked decrease of HIV-1 gap p24 release and reduction in reverse transcriptase activity was observed when chronically HIV-infected ACH-2 lymphocytes were treated with coumarins (ED50% range 10(-6)-10(-9) mol/l). However, the intracellular composition of HIV-1 core proteins in drug-exposed cells was not modified. Results suggest that although no complete inhibition of viral production has been observed in vitro this class of drugs may present potential interest as antiviral agents.

    Topics: 4-Hydroxycoumarins; Cell-Free System; Coumarins; HIV Core Protein p24; HIV-1; Humans; Lymphocytes; Transcription, Genetic; Umbelliferones; Virus Replication; Warfarin

1993
The preferred solution conformation of warfarin at the active site of cytochrome P-450 based on the CD spectra in octanol/water model system.
    Journal of medicinal chemistry, 1984, Volume: 27, Issue:8

    An octanol/water model system and circular dichroism (CD) spectroscopy have been used to study the solution conformation of warfarin in aqueous and lipid environments. Upon partitioning of (S)-warfarin from buffer pH 7.4 into octanol, the position of the absorption band due to the alpha, beta-unsaturated carbonyl chromophore shifts from 210 nm in the aqueous phase to 220 nm in the octanol phase. The shift is coupled to an increase in the molecular ellipticity of the band, suggesting the formation of a dissymmetric chromophore. Comparison of CD spectra of conformationally fixed analogues of warfarin to that of warfarin in solution suggests that the compound shifts from the open side chain keto form in the aqueous phase at pH 7.4 to the cyclic hemiketal form after partitioning into the lipid octanol phase. On the basis of these results, the hemiketal form is proposed as the preferred solution conformation of warfarin in the lipid environment of the active site of cytochrome P-450 and the relationship between solution conformation and stereoselectivity of warfarin metabolism by beta-naphthoflavone inducible cytochrome P-450 is discussed.

    Topics: 4-Hydroxycoumarins; Binding Sites; Circular Dichroism; Cytochrome P-450 Enzyme System; Models, Chemical; Octanols; Protein Conformation; Warfarin; Water

1984