Synthesis and biological activities of hapalosin derivatives with modification at the C12 position.
Among the hapalosin derivatives synthesized, the compounds carrying methyl (5a), methylthioethyl (5d) and phenylmethyl (5e) groups at the C12 position possess only the cis-peptide structure, in contrast to the cases of 5b and 5c. In addition to their conformational stability, the biological activities of the compounds were determined in relation of the P-glycoprotein-mediated MDR-reversing activity and induction of apoptosis.
Kashihara
N
N
Department of Chemistry, Faculty of Science and Technology, Keio University, Hiyoshi, Yokohama, Japan.
To-e
S
S
Nakamura
K
K
Umezawa
K
K
Yamamura
S
S
Nishiyama
S
S
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D047630:Depsipeptides; D018432:Drug Resistance, Multiple; D007769:Lactams / Q000737:chemistry* / Q000494:pharmacology; D007783:Lactones / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000494:pharmacology; D011487:Protein Conformation; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000378:metabolism
D000970:Antineoplastic Agents; D047630:Depsipeptides; D007769:Lactams; D007783:Lactones; D010456:Peptides, Cyclic; C111358:hapalosin; D014750:Vincristine