title: Chemical synthesis and biological evaluation of palmerolide A analogues.
abstract: 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.
authors.affiliation: Chemical Synthesis Laboratory@Biopolis, Institute of Chemical and Engineering Sciences(ICES), Agency for Science, Technology and Research (A*STAR), Singapore. kcn@scripps.edu
authors.forename: K C
authors.initials: KC
authors.lastname: Nicolaou
authors.forename: Gulice Y C
authors.initials: GY
authors.lastname: Leung
authors.forename: Dattatraya H
authors.initials: DH
authors.lastname: Dethe
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Guduru
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Sun
authors.forename: Chek Shik
authors.initials: CS
authors.lastname: Lim
authors.forename: David Y-K
authors.initials: DY
authors.lastname: Chen
mesh_terms: 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
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D018942:Macrolides; D011090:Polyenes; C522534:palmerolide A; D000251:Adenosine Triphosphatases