Human colorectal carcinoma cells in vitro as a means to assess the metabolism of analogs of mycophenolic acid.

摘要: Cultures of the human colorectal carcinoma line, HT29, were used to assess susceptibility glucuronidation cytostatic, immunosuppressive drug mycophenolic acid (MPA) and 19 its analogs. Removal metabolically vulnerable 7-hydroxyl group or replacement by a fluorine atom, amino group, nitrile resulted in compounds that completely resistant metabolism, but had substantially lower antiproliferative potency against EMT6 line is unable glucuronidate MPA. In retaining 7-hydroxy function lactone moiety phthalane ring MPA either cyclopentanone 6-membered lactam afforded some protection also partially suppressed activity. Some lipophilic substituents at position 2 hexenoic side chain analogs with increased whereas several steric bulk this (including benzyl, p-hydroxyphenyl, trifluoroacetamidophenyl,S-methyl, methoxymethyl) markedly inhibited metabolism. The last three these derivatives maintained exceeded We suggest cultures cells lines may provide rapid convenient means assessing novel synthetic both phase I II metabolic conversions.