Perturbing effects of carvedilol on a model membrane system: role of lipophilicity and chemical structure.
Carvedilol, a beta-adrenergic blocker used to treat cardiovascular diseases, protects cell membranes from lipid peroxidative damage. Previous studies suggested the drug resides in a non-polar environment and partitions into cell membranes, perturbing their fluidity. Here differential scanning calorimetry (DSC) and fluorescence spectroscopy were applied to further investigate interactions of carvedilol with a liposome model. Results indicate the association is relatively unaffected by pH or temperature, but could be sensitive to liposome composition. The drug's carbazole group plays the dominant role in bilayer perturbation. Compared with other beta-blockers examined, carvedilol produced the strongest liposome DSC perturbation. Locations of carbazole and carvedilol in the liposome were determined using depth-dependent fluorescent probes. Both compounds are situated in the middle of the bilayer, consistent with strong hydrophobic interactions. This combination of high lipophilicity and specific chemical structure appear required for carvedilol's novel antioxidant activity, and may enhance cardioprotection.
Butler
Stephanie
S
Department of Chemistry 016-00, Temple University, Philadelphia, PA 19122, USA.
Wang
Rongwei
R
Wunder
Stephanie L
SL
Cheng
Hung-Yuan
HY
Randall
Cynthia S
CS
D000319:Adrenergic beta-Antagonists / Q000737:chemistry* / Q000378:metabolism; D002152:Calorimetry, Differential Scanning; D002227:Carbazoles / Q000737:chemistry* / Q000378:metabolism; D000077261:Carvedilol; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D005456:Fluorescent Dyes; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes; D008560:Membrane Fluidity; D008563:Membrane Lipids / Q000737:chemistry*; D008954:Models, Biological; D008958:Models, Molecular; D011412:Propanolamines / Q000737:chemistry* / Q000378:metabolism; D013050:Spectrometry, Fluorescence
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D005456:Fluorescent Dyes; D008051:Lipid Bilayers; D008081:Liposomes; D008563:Membrane Lipids; D011412:Propanolamines; D000077261:Carvedilol; C041514:carbazole