Molecules 2011, 16(11), 9404-9420; doi:10.3390/molecules16119404

Succinobucol’s New Coat — Conjugation with Steroids to Alter Its Drug Effect and Bioavailability

1 Department of Chemistry, FI-40014, University of Jyväskylä, P.O. Box 35, Finland 2 Isotope Laboratory, Institute of Experimental Botany, Academy of Sciences of the Czech Republic, Vídeňská 1083, 14220, Prague 4, Czech Republic 3 Institute of Chemical Technology, Prague, Technická 5, 16628, Prague 6, Czech Republic 4 Department of Spectroscopy and Physical Organic Chemistry, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 16610, Prague 6, Czech Republic 5 Palacký University in Olomouc, Institute of Translational and Molecular Medicine, Hněvotínská 3, 77515, Olomouc, Czech Republic
* Author to whom correspondence should be addressed.
Received: 29 September 2011; in revised form: 2 November 2011 / Accepted: 7 November 2011 / Published: 10 November 2011
(This article belongs to the Special Issue Steroids)
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Abstract: Synthesis, detailed structural characterization (X-ray, NMR, MS, IR, elemental analysis), and studies of toxicity, antioxidant activity and bioavailability of unique potent anti-atherosclerotic succinobucol-steroid conjugates are reported. The conjugates consist of, on one side, the therapeutically important drug succinobucol ([4-{2,6-di-tert-butyl-4-[(1-{[3-tert-butyl-4-hydroxy-5-(propan-2-yl)phenyl]sulfanyl}ethyl)sulfanyl]phenoxy}-4-oxo-butanoic acid]) possessing an antioxidant and anti-inflammatory activity, and on the other side, plant stanol/sterols (stigmastanol, β-sitosterol and stigmasterol) possessing an ability to lower the blood cholesterol level. A cholesterol-succinobucol prodrug was also prepared in order to enhance the absorption of succinobucol through the intestinal membrane into the organism and to target the drug into the place of lipid metabolism—The enterohepatic circulation system. Their low toxicity towards mice fibroblasts at maximal concentrations, their antioxidant activity, comparable or even higher than that of ascorbic acid as determined by direct quenching of the DPPH radical, and their potential for significantly altering total and LDL cholesterol levels, suggest that these conjugates merit further studies in the treatment of cardiovascular or other related diseases. A brief discussion of succinobucol’s ability to quench the radicals, supported with a computational model of the electrostatic potential mapped on the electron density surface of the drug, is also presented.
Keywords: succinobucol; phytosterol; atherosclerosis; cholesterol; probucol

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MDPI and ACS Style

Jurček, O.; Ikonen, S.; Buřičová, L.; Wimmerová, M.; Wimmer, Z.; Drašar, P.; Horníček, J.; Galandáková, A.; Ulrichová, J.; Kolehmainen, E.T. Succinobucol’s New Coat — Conjugation with Steroids to Alter Its Drug Effect and Bioavailability. Molecules 2011, 16, 9404-9420.

AMA Style

Jurček O, Ikonen S, Buřičová L, Wimmerová M, Wimmer Z, Drašar P, Horníček J, Galandáková A, Ulrichová J, Kolehmainen ET. Succinobucol’s New Coat — Conjugation with Steroids to Alter Its Drug Effect and Bioavailability. Molecules. 2011; 16(11):9404-9420.

Chicago/Turabian Style

Jurček, Ondřej; Ikonen, Satu; Buřičová, Lucie; Wimmerová, Martina; Wimmer, Zdeněk; Drašar, Pavel; Horníček, Jan; Galandáková, Adéla; Ulrichová, Jitka; Kolehmainen, Erkki T. 2011. "Succinobucol’s New Coat — Conjugation with Steroids to Alter Its Drug Effect and Bioavailability." Molecules 16, no. 11: 9404-9420.

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