[Show abstract][Hide abstract] ABSTRACT: Carotenoids have been implicated in numerous epidemiological studies as being protective against cancer at many sites, and their chemopreventive properties have been confirmed in laboratory studies. Astaxanthin (AST), primarily a carotenoid of marine origin, responsible for the pink coloration of salmon, shrimp and lobster, has received relatively little attention. As with other carotenoids, its highly lipophilic properties complicate delivery to model systems. To overcome this issue we have synthesized a novel tetrasodium diphosphate astaxanthin (pAST) derivative with aqueous dispersibility of 25.21 mg/ml. pAST was delivered to C3H/10T1/2 cells in an aqueous/ethanol solution and compared with non-esterified AST dissolved in tetrahydrofuran. We show pAST to (i) upregulate connexin 43 (Cx43) protein expression; (ii) increase the formation of Cx43 immunoreactive plaques; (iii) upregulate gap junctional intercellular communication (GJIC); and (iv) cause 100% inhibition of methylcholanthrene-induced neoplastic transformation at 10(-6) M. In all these assays, pAST was superior to non-esterified AST itself; in fact, pAST exceeded the potency of all other previously tested carotenoids in this model system. Cleavage of pAST to non-esterified (free) AST and uptake into cells was also verified by HPLC; however, levels of free AST were approximately 100-fold lower than in cells treated with AST itself, suggesting that pAST possesses intrinsic activity. The dual properties of water dispersibility (enabling parenteral administration in vivo) and increased potency should prove extremely useful in the future development of cancer chemopreventive agents.
[Show abstract][Hide abstract] ABSTRACT: A practical procedure is described for the multigram preparation of disodium disuccinate derivatives of synthetic astaxanthin (Cardax) [from all-trans-(all-E)-3S,3‘S-, meso-(3R,3‘S)-, and 3R,3‘R-dihydroxy-β,β-carotene-4,4‘-dione) in a 1:2:1 statistical mixture of stereoisomers, as well as from the individual component stereoisomers]. Process development eliminated chromatographic separations, controlled geometric isomerization, and improved the overall yield of the two-step process, with significant improvements in both the yield and purity of Cardax. Bulk chromatographic separation of the diastereomeric dicamphanic acid ester of synthetic astaxanthin was performed by modifications of the published procedure to subsequently generate multigram quantities of each stereoisomer of disodium disuccinate of astaxanthin.
Organic Process Research & Development 08/2004; 8(5). DOI:10.1021/op049909i · 2.55 Impact Factor