Synthesis and evaluation of hapalosin and analogs as MDR-reversing agents.
The marine natural product hapalosin and 22 analogs, which incorporated systematic substituent deletions or variations, were prepared. These compounds were evaluated in a cell-based assay for both MDR-reversing activity and general cytotoxicity. Some substituent modifications resulted in lower cytotoxicities, but most structural changes were either detrimental to or did not seriously alter the MDR-reversing activity.
O'Connell
C E
CE
Eisai Research Institute, Andover, MA 01810, USA.
Salvato
K A
KA
Meng
Z
Z
Littlefield
B A
BA
Schwartz
C E
CE
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D047630:Depsipeptides; D018432:Drug Resistance, Multiple; D006801:Humans; D020128:Inhibitory Concentration 50; D007769:Lactams / Q000138:chemical synthesis*; D007783:Lactones / Q000138:chemical synthesis*; D051379:Mice; D008956:Models, Chemical; D011994:Recombinant Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D047630:Depsipeptides; D007769:Lactams; D007783:Lactones; D011994:Recombinant Proteins; C111358:hapalosin