Ih. Hall et al., SYNTHESIS AND CYTOTOXIC ACTION OF 3,5-ISOXAZOLIDINEDIONES AND 2-ISOXAZOLIN-5-ONES IN MURINE AND HUMAN TUMORS, Archiv der pharmazie, 330(3), 1997, pp. 67-73
The 3,5-isoxazolidmediones and 2-isoxazonn-3-ones demonstrated potent
cytotoxicity against the growth of human Tmolt(3) T cell leukemia, mur
ine P388 and L1210 leukemias as well as human HeLa-S-3 uterine carcino
ma and glioma tumor cell growth. The specificity of the 3,5-isoxazolid
inedione and 2-isoxazoline-5-one derivatives as cytotoxic agents varie
d with the histological type of tumor cell, Selected compounds were ac
tive against solid HeLa uterine, KB nasopharynx, skin A431, SW-480 ade
nocarcinoma, osteosarcoma and glioma growth. Selected compounds demons
trated in vivo antineoplastic activity against Ehrlich ascites carcino
ma growth. In L-1210 leukemia cells, the agents blocked DNA and protei
n synthesis at 25, 50 and 100 mu M over 60 min The agents were effecti
ve in reducing rate limiting enzymes in the de novo purine and pyrimid
ine pathways, In addition they suppressed dihydrofolate reductase and
ribonucleoside reductase activities with moderate inhibition of DNA an
d RNA polymerase activities, DNA itself was not a target of the agents
.