Chemical synthesis and biological evaluation of palmerolide A analogues.
Molecular design and chemical synthesis of several palmerolide A analogues allowed the first structure activity relationships (SARs) of this newly discovered marine antitumor agent. From several analogues synthesized and tested (ent- 1, 5- 14, 21- 26, 50, 51), compounds 25 (with a phenyl substituent on the side chain) and 51 (lacking the C-7 hydroxyl group) were the most interesting, exhibiting approximately a 10-fold increase in potency and equipotency, respectively, to the natural product. These findings point the way to more focused structure activity relationship studies.
Nicolaou
K C
KC
Chemical Synthesis Laboratory@Biopolis, Institute of Chemical and Engineering Sciences(ICES), Agency for Science, Technology and Research (A*STAR), Singapore. kcn@scripps.edu
Leung
Gulice Y C
GY
Dethe
Dattatraya H
DH
Guduru
Ramakrishna
R
Sun
Ya-Ping
YP
Lim
Chek Shik
CS
Chen
David Y-K
DY
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D018942:Macrolides / Q000138:chemical synthesis* / Q000494:pharmacology*; D011090:Polyenes / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000577:Amides; D004791:Enzyme Inhibitors; D018942:Macrolides; D011090:Polyenes; C522534:palmerolide A; D000251:Adenosine Triphosphatases