Synthesis of psymberin analogues: probing a functional correlation with the pederin/mycalamide family of natural products.
In this letter we describe an efficient synthesis of "psympederin", a hybrid between the novel antitumor natural product psymberin and the blister beetle toxin pederin. Evaluation of antiproliferative activity reveals that the dihydroisocoumarin fragment is important for psymberin toxicity and the cyclic pederate fragment is important for pederin/mycalamide toxicity. On the basis of preliminary results described herein, we speculate that, despite their structural resemblance, psymberin and pederin/mycalamide induce toxicity through different mechanisms. [reaction: see text].
Jiang
Xin
X
Department of Biochemistry, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038, USA.
Williams
Noelle
N
De Brabander
Jef K
JK
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003374:Coumarins; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D011714:Pyrans / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D011753:Pyrones / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship
D003374:Coumarins; D011714:Pyrans; D011753:Pyrones; C059647:mycalamide B; C498383:psymberin; C518008:psympederin; C059646:mycalamide A; C100127:pederin