Cytotoxic Michael-type amine adducts of alpha-methylene lactones alantolactone and isoalantolactone.
Two series of cytotoxic (IC50, K562 cell line, 1-24 microM) alpha-aminomethyl substituted lactones 3 and 4 were prepared by stereoselective Michael-type addition of amines to alantolactone (1) and isoalantolactone (2). The lactones 1 and 2 and their amine adducts induce apoptosis and act as alkylating agents.
Lawrence
N J
NJ
Department of Chemistry, UMIST, Manchester, UK. lawrencenj1@cardiff.ac.uk
McGown
A T
AT
Nduka
J
J
Hadfield
J A
JA
Pritchard
R G
RG
D000588:Amines / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D007783:Lactones / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000588:Amines; D000970:Antineoplastic Agents; D007783:Lactones; C416683:methylene-lactone