Enantioselective synthesis and biological activity of (3S,4R)- and (3S,4S)-3-hydroxy-4-hydroxymethyl- 4-butanolides in relation to PGE2.
Compounds 9 and 13 were synthesized, and their structures and stereochemistry were elucidated by spectroscopic methods. In competition binding experiments, specific [(3)H]-PGE(2) binding was significantly displaced by compound 9 and, to a lesser extent, by 13, in a dose-dependent manner. The biological properties of compound 9 were studied on HL-60 cells, and several effects were found related to those of PGE(2). Compound 9 increases c-fos mRNA level as does PGE(2) and antagonizes TPA-induced terminal differentiation.
Miranda
Pedro O
PO
Instituto Universitario de Bio-Orgánica Antonio González-Instituto de Productos Naturales y Agrobiología-CSIC, Avenida Astrofísico F. Sánchez 3, 38206 La Laguna, Tenerife, Canary Islands, Spain.
Estévez
Francisco
F
Quintana
José
J
García
Candelaria I
CI
Brouard
Ignacio
I
Padrón
Juan I
JI
Pivel
Juan P
JP
Bermejo
Jaime
J
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001667:Binding, Competitive; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015232:Dinoprostone / Q000737:chemistry / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D011869:Radioligand Assay; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; D015107:4-Butyrolactone