Preparation and cytotoxicity evaluation of acetylated fijianolides (a.k.a. laulimalide)

The fijianolides (a.k.a. laulimalides) discovered in the 1980s at UC Santa Cruz and U. Hawaii continue to attract attention as a unique class of sponge-derived polyketides. They’ve shown low nanomolar cytotoxicity against human tumor cell lines. A mechanism for this activity is their ability to stabilize microtubles at a similar but distinct site to that of the anti-cancer drug Taxol®. Fijianolide B (2, aka laulimalide), which is extremely bioactive was the subject of two in vivo studies by different labs and resulted in different outcomes. One study reported significant inhibition of growth of solid tumors over 28 days without toxicity.1 While another reported minimal inhibition of solid tumor growth accompanied by significant toxicity.2 We have launched a new campaign to re-examine this dichotomy and create a more stable pre-clinical candidate, because 2 rearranges over time to the much less active 1. In this poster we describe the preparation of diacetylated analogs of 1 and 2, and their relative bioactivites against HCT-116 and PANC-1 tumor cell lines.
¹ Johnson et. al., 2007, J. Med. Chem. 50, 3795-3803.  
² Liu et. al., 2007, Anticancer Res. 27, 1509-1518.