The cytotoxic activity of cyclic imido alkyl ethers, thioethers, sulfoxides, sulfones and related derivatives.
Cyclic imides such as N-substituted alkyl ethers, thioethers, sulfoxides, sulfones and related derivatives were potent agents against human single cell tumors and selected solid tumor growths, eg adenocarcinoma of the colon and glioma. These agents in the L1210 lymphoid leukemia tumor model preferentially inhibited DNA synthesis. The regulatory enzyme sites in the purine pathway were targets of the agents. Other sites of inhibition were DNA polymerase alpha and thymidylate synthetase activities. d(NTP) pool levels were also reduced by the agents over 60 min.
Hall
I H
IH
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina at Chapel Hill 27599.
Chapman
J M
JM
Wong
O T
OT
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007094:Imides / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D007094:Imides