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Day, Daniel R; Jabaiah, Suraya; Jacobs, Robert S; Little, R Daniel
Marine drugs, 08/2013, Letnik: 11, Številka: 9Journal Article
Pseudopterosin A (PsA) treatment of growth factor depleted human umbilical vein endothelial cell (HUVEC) cultures formulated in hydroxypropyl-β-cyclodextrin (HPβCD) for 42 h unexpectedly produced a 25% increase in cell proliferation (EC₅₀ = 1.34 × 10⁻⁸ M). Analysis of dose response curves revealed pseudo-first order saturation kinetics, and the uncoupling of cytotoxicity from cell proliferation, thereby resulting in a widening of the therapeutic index. The formulation of PsA into HPβCD produced a 200-fold increase in potency over a DMSO formulation; we propose this could result from a constrained presentation of PsA to the receptor, which would limit non-specific binding. These results support the hypothesis that the non-specific receptor binding of PsA when formulated in DMSO has ostensibly masked prior estimates of specific activity, potency, and mechanism. Collectively, these results suggest that the formulation of PsA and compounds of similar chemical properties in HPβCD could result in significant pharmacological findings that may otherwise be obscured when using solvents such as DMSO.
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in: SICRIS
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