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Synthesis and Cytotoxic Action of 3,5‐Isoxazolidinediones and 2‐Isoxazolin‐5‐ones in Murine and Human Tumors
Author(s) -
Hall Iris H.,
Izydore Robert A.,
Zhou Xaioming,
Daniels Dwayne L.,
Woodard Tyrone,
Debnath Manik L.,
Tse Elaine,
Muhammad Rosallah A.
Publication year - 1997
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.19973300306
Subject(s) - hela , dna synthesis , cytotoxic t cell , cytotoxicity , dihydrofolate reductase , ehrlich ascites carcinoma , biology , purine , microbiology and biotechnology , cancer research , in vivo , biochemistry , cell growth , dna , glioma , chemistry , enzyme , in vitro
The 3,5‐isoxazolidinediones and 2‐isoxazolin‐5‐ones demonstrated potent cytotoxicity against the growth of human Tmolt 3 T cell leukemia, murine P388 and L1210 leukemias, as well as human HeLa‐S 3 uterine carcinoma and glioma tumor cell growth. The specificity of the 3,5‐isoxazolidinedione and 2‐isoxazoline‐5‐one derivatives as cytotoxic agents varied with the histological type of tumor cell. Selected compounds were active against solid HeLa uterine, KB nasopharynx, skin A431, SW‐480 adenocarcinoma, osteosarcoma and glioma growth. Selected compounds demonstrated in vivo antineoplastic activity against Ehrlich ascites carcinoma growth. In L‐1210 leukemia cells, the agents blocked DNA and protein synthesis at 25,50 and 100 μM over 60 min. The agents were effective in reducing rate limiting enzymes in the de novo purine and pyrimidine pathways. In addition they suppressed dihydrofolate reductase and ribonucleoside reductase activities with moderate inhibition of DNA and RNA polymerase activities. DNA itself was not a target of the agents.