Antitumor activity of two novel low immunosuppressive fluoropyrimidines UK-21 and UK-25.

Abstract

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 1-(6-[N-(2-n-propyl-n-pentanoyl)-glycyl]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 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.

• Authors: O Sakamoto, H Mori, K Kitaichi, A Koda, T Kato
• Journal: Japanese journal of pharmacology (Jpn J Pharmacol) Vol. 59 Issue 4 Pg. 469-76 (Aug 1992) ISSN: 0021-5198 [Print] Japan
• PMID: 1434142 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• UK 21
• UK 25
• Tegafur
• Methylcholanthrene
• Glycine
• Fluorouracil
• Uridine

Topics

• Administration, Oral
• Animals
• Antineoplastic Agents (pharmacology)
• Body Weight (drug effects)
• Fluorouracil (analogs & derivatives, pharmacology)
• Glycine (analogs & derivatives, pharmacology)
• Leukemia L1210 (drug therapy)
• Leukemia P388 (drug therapy)
• Lung Neoplasms (drug therapy)
• Methylcholanthrene
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Inbred DBA
• Neoplasm Transplantation
• Neoplasms, Experimental (chemically induced, drug therapy)
• Organ Size (drug effects)
• Sarcoma 180 (drug therapy)
• Spleen (anatomy & histology, drug effects)
• Tegafur (pharmacology)
• Thymus Gland (anatomy & histology, drug effects)
• Uridine (analogs & derivatives, pharmacology)