Design, synthesis and evaluation of bouvardin, deoxybouvardin and RA-I-XIV pharmacophore analogs.
The synthesis and in vitro cytotoxic evaluation of a key set of cycloisodityrosine subunit analogs of deoxybouvardin and RA-VII are detailed and constitute a complete investigation of the natural product pharmacophore. The studies illustrate that the 18-membered ring tetrapeptide potentiation of the cytotoxic activity of cycloisodityrosine is not likely to be due to simple alteration or constraint of the conformation of the 14-membered cycloisodityrosine subunit and that simple derivatization of cycloisodityrosine may not provide the same potentiation.
Boger
D L
DL
Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037.
Patane
M A
MA
Jin
Q
Q
Kitos
P A
PA
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D066298:In Vitro Techniques; D007939:Leukemia L1210 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D010456:Peptides, Cyclic; C018234:bouvardin; C043547:RA V