Nigricanosides A and B, Antimitotic Glycolipids Isolated from the Green Alga Avrainvillea nigricans Collected in Dominica

The methyl esters 3 and 4 of the antimitotic glycolipids nigricanosides A (1) and B (2) have been isolated from extracts of the green alga Avrainvillea nigrans collected in Dominica. The structures of 3 and 4 were elucidated by detailed analysis of MS and NMR data. Nigricanoside A dimethyl ester 3 arrests human breast cancer MCF-7 cells in mitosis with an IC₅₀ of 3 nM. Arrested cells have highly disorganized microtubule spindles, compared with the bipolar spindles of untreated metaphase cells. Ester 3 at 20 μM stimulates the polymerization of pure tubulin in vitro and it inhibits the proliferation of both MCF-7 and human colon cancer HCT-116 cells with an IC₅₀ ≈ 3 nM. The nigricanosides are the first examples of a new class of ether-linked glycoglycerolipids. The potent antimitotic activity of the nigricanosides and their ability to promote tubulin polymerization is without precedent among previously known glycoglycerolipids.