Antitumor Activity of Two Novel Low Immunosuppressive Fluoropyrimidines UK-21 and UK-25

• Published in: Japanese Journal of Pharmacology 1992, Vol.59(4), pp.469-476
• Main Authors: Sakamoto, Osami, Mori, Hiroshi, Kitaichi, Kiyoyuki, Koda, Akihide, Kato, Taketoshi
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; 5-Fluorouridine; Administration, Oral; Animals; Antineoplastic agents; Antineoplastic Agents - pharmacology; Biological and medical sciences; Body Weight - drug effects; Fluorouracil - analogs & derivatives; Fluorouracil - pharmacology; General aspects; Glycine - analogs & derivatives; Glycine - pharmacology; Leukemia L1210 - drug therapy; Leukemia P388 - drug therapy; Lung Neoplasms - drug therapy; Medical sciences; Methylcholanthrene; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred DBA; Neoplasm Transplantation; Neoplasms, Experimental - chemically induced; Neoplasms, Experimental - drug therapy; Organ Size - drug effects; Pharmacology. Drug treatments; Sarcoma 180 - drug therapy; Spleen - anatomy & histology; Spleen - drug effects; Tegafur - pharmacology; Thymus Gland - anatomy & histology; Thymus Gland - drug effects; UK-21; UK-25; Uridine - analogs & derivatives; Uridine - pharmacology
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1254/jjp.59.469

We have previously reported that 2’,3’,5’-tris-O-[N-(2-n-propyl-n-pentanoyl)glycyl]-5-fluorouridine (UK-21), a derivative of 5-fluorouridine (5-FUR), and l-{6-[N-(2-n-propyl-n-pentanoyl)-gIycyl]amino-n-hexylcarbamoyl}-5-fluorouracil (UK-25), a derivative of 5-fluorouracil (5-FU), exert their antitumor activity in mice bearing Meth A or EL4 tumor, while their immunosuppressive effects are mild. In the present study, we examined the effects of these compounds on Sarcoma-180 (S-180), P388, L1210, and Lewis lung carcinoma (LLC) in mice by p.o. administration and on Meth A tumor by i.p.-administration. UK-21 given p.o. showed an antitumor effect against S-180, but it showed virtually no antitumor effects against P388, L1210 and LLC. UK-21 given i.p., on the other hand, strongly inhibited the growth of Meth A tumor at a far lower dose than that for oral administration. The bioavailability of UK-21 given p.o. was suspected to be poor. UK-25 given p.o., in contrast, showed the antitumor effect on all of the tumors employed. The bioavailability of UK-25 given p.o. seemed to be comparable to those of other drugs. These results suggest that UK-21 has the potential for development as a parenterally applicable anticancer drug, and UK-25 has the potential as an oral one.