title: Succinobucol's new coat--conjugation with steroids to alter its drug effect and bioavailability.
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.
authors.affiliation: Department of Chemistry, FI-40014, University of Jyväskylä, P.O. Box 35, Finland. jurcekondrej@gmail.com
authors.forename: Ondřej
authors.initials: O
authors.lastname: Jurček
authors.forename: Satu
authors.initials: S
authors.lastname: Ikonen
authors.forename: Lucie
authors.initials: L
authors.lastname: Buřičová
authors.forename: Martina
authors.initials: M
authors.lastname: Wimmerová
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Wimmer
authors.forename: Pavel
authors.initials: P
authors.lastname: Drašar
authors.forename: Jan
authors.initials: J
authors.lastname: Horníček
authors.forename: Adéla
authors.initials: A
authors.lastname: Galandáková
authors.forename: Jitka
authors.initials: J
authors.lastname: Ulrichová
authors.forename: Erkki T
authors.initials: ET
authors.lastname: Kolehmainen
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D000975:Antioxidants / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D001682:Biological Availability; D001713:Biphenyl Compounds / Q000737:chemistry; D002986:Clinical Trials as Topic; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005609:Free Radicals / Q000737:chemistry; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D010851:Picrates / Q000737:chemistry; D011341:Probucol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D055672:Static Electricity; D013256:Steroids / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000633:toxicity
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D001713:Biphenyl Compounds; D005609:Free Radicals; D010851:Picrates; D013256:Steroids; C004931:1,1-diphenyl-2-picrylhydrazyl; C471047:succinobucol; D011341:Probucol
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