Antitumor activity of two novel low immunosuppressive fluoropyrimidines UK-21 and UK-25.
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.
Sakamoto
O
O
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Mori
H
H
Kitaichi
K
K
Koda
A
A
Kato
T
T
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D008175:Lung Neoplasms / Q000188:drug therapy; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy; D009929:Organ Size / Q000187:drug effects; D012510:Sarcoma 180 / Q000188:drug therapy; D013154:Spleen / Q000033:anatomy & histology / Q000187:drug effects; D005641:Tegafur / Q000494:pharmacology; D013950:Thymus Gland / Q000033:anatomy & histology / Q000187:drug effects; D014529:Uridine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000970:Antineoplastic Agents; C078136:UK 21; C078137:UK 25; D005641:Tegafur; D008748:Methylcholanthrene; D005998:Glycine; D005472:Fluorouracil; D014529:Uridine