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Article

Cyclodextrin Formulation of the Marine Natural Product Pseudopterosin A Uncovers Optimal Pharmacodynamics in Proliferation Studies of Human Umbilical Vein Endothelial Cells

1
Department of Ecology, Evolution, and Marine Biology, University of California, Santa Barbara, CA 93106, USA
2
Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106, USA
3
Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA 93106, USA
*
Author to whom correspondence should be addressed.
Mar. Drugs 2013, 11(9), 3258-3271; https://doi.org/10.3390/md11093258
Received: 5 July 2013 / Revised: 13 August 2013 / Accepted: 14 August 2013 / Published: 26 August 2013
(This article belongs to the Special Issue Marine Secondary Metabolites)
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. View Full-Text
Keywords: pseudopterosins; log P; human umbilical vein endothelial cells (HUVEC); proliferation; hydroxypropyl-beta-cyclodextrin (HPβCD) pseudopterosins; log P; human umbilical vein endothelial cells (HUVEC); proliferation; hydroxypropyl-beta-cyclodextrin (HPβCD)
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MDPI and ACS Style

Day, D.R.; Jabaiah, S.; Jacobs, R.S.; Little, R.D. Cyclodextrin Formulation of the Marine Natural Product Pseudopterosin A Uncovers Optimal Pharmacodynamics in Proliferation Studies of Human Umbilical Vein Endothelial Cells. Mar. Drugs 2013, 11, 3258-3271. https://doi.org/10.3390/md11093258

AMA Style

Day DR, Jabaiah S, Jacobs RS, Little RD. Cyclodextrin Formulation of the Marine Natural Product Pseudopterosin A Uncovers Optimal Pharmacodynamics in Proliferation Studies of Human Umbilical Vein Endothelial Cells. Marine Drugs. 2013; 11(9):3258-3271. https://doi.org/10.3390/md11093258

Chicago/Turabian Style

Day, Daniel R., Suraya Jabaiah, Robert S. Jacobs, and R. D. Little 2013. "Cyclodextrin Formulation of the Marine Natural Product Pseudopterosin A Uncovers Optimal Pharmacodynamics in Proliferation Studies of Human Umbilical Vein Endothelial Cells" Marine Drugs 11, no. 9: 3258-3271. https://doi.org/10.3390/md11093258

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