Membrane-permeant, bioactivatable analogues of cGMP as inducers of cell death in IPC-81 leukemia cells.
We report an improved single-step synthesis to generate the membrane-permeant acetoxymethyl esters (AM-esters) of cGMP and three cGMP-analogues. These bioactivatable compounds were found to induce cell death in rat IPC-81 cells, a model system for acute myelocytic leukemia, in micromolar doses, while the corresponding non-modified cGMP-analogues were inactive.
Schwede
F
F
Zentrum für Umweltforschung und -technologie, Abt. Bioorganische Chemie, Universität Bremen, Germany.
Brustugun
O T
OT
Zorn-Kruppa
M
M
Døskeland
S O
SO
Jastorff
B
B
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D001711:Biotransformation; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007942:Leukemia, Experimental / Q000188:drug therapy*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy; D051381:Rats; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; C016276:8-bromocyclic GMP; D006152:Cyclic GMP