The effect of structural modifications of 5-fluorouracil derivatives on their transport and biodegradation by isolated rat jejunum.
The continuous-perfusion technique was used in an isolated segment of everted rat jejunum to study transport and biotransformation processes in a series of cancerostatic derivatives of 5-fluorouracil. Metabolic alterations during penetration of the intestinal wall were assessed by high-performance liquid chromatography (HPLC). Octanol-buffer partition coefficients were measured, and the lipophilicity of the study compounds and fragmental constants for their sugar moieties were assessed. In the present series of 5-fluorouracil derivatives, there was no correlation between lipophilicity and metabolic cleavage to 5-fluorouracil, but a correlation was found between lipophilicity and the transport rate. Remarkable stability of the nucleoside bond and high biotransport were observed with 5'-chloro-5-fluorouridine, suggesting a different mode of activation for this derivative.
Novotný
L
L
Cancer Research Institute, Slovak Academy of Sciences, Bratislava.
Farghali
H
H
Janků
I
I
Beránek
J
J
D000818:Animals; D001673:Biodegradation, Environmental; D001692:Biological Transport; D050260:Carbohydrate Metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism*; D050356:Lipid Metabolism; D010477:Perfusion / Q000379:methods; D051381:Rats; D012704:Serous Membrane / Q000378:metabolism; D013329:Structure-Activity Relationship
D005472:Fluorouracil