title: Mimicking the lipid peroxidation inhibitory activity of phospholipid hydroperoxide glutathione peroxidase (GPx4) by using fatty acid conjugates of a water-soluble selenolane.
abstract: A series of fatty acid conjugates of trans-3,4-dihydroxy-1-selenolane (DHS) were synthesized by reacting DHS with appropriate acid chlorides. The obtained monoesters were evaluated for their antioxidant capacities by the lipid peroxidation assay using a lecithin/cholesterol liposome as a model system. The observed antioxidant capacities against accumulation of the lipid hydroperoxide (LOOH) increased with increasing the alkyl chain length and became saturated for dodecanoic acid (C12) or higher fatty acid monoesters, for which the capacities were much greater than those of DHS, its tridecanoic acid (C13) diester, and PhSeSePh. On the other hand, the bacteriostatic activity of myristic acid (C14) monoester, evaluated through the colony formation assay using Bacillus subtilis, indicated that it has higher affinity to bacterial cell membranes than parent DHS. Since DHS-fatty acid conjugates would inhibit lipid peroxidation through glutathione peroxidase (GPx)-like 2e- mechanism, higher fatty acid monoesters of DHS can mimic the function of GPx4, which interacts with LOOH to reduce it to harmless alcohol (LOH). Importance of the balance between hydrophilicity and lipophilicity for the design of effective GPx4 mimics was suggested.
authors.affiliation: Department of Chemistry, School of Science, Tokai University, Kitakaname, Hiratsuka-shi, Kanagawa 259-1292, Japan. miwaoka@tokai.ac.jp.
authors.forename: Michio
authors.initials: M
authors.lastname: Iwaoka
authors.affiliation: Department of Chemistry, School of Science, Tokai University, Kitakaname, Hiratsuka-shi, Kanagawa 259-1292, Japan. puing1103@gmail.com.
authors.forename: Arisa
authors.initials: A
authors.lastname: Katakura
authors.affiliation: Department of Chemistry, School of Science, Tokai University, Kitakaname, Hiratsuka-shi, Kanagawa 259-1292, Japan. j-mishima@kofu.tokai.ed.jp.
authors.forename: Jun
authors.initials: J
authors.lastname: Mishima
authors.affiliation: Department of Chemistry, School of Science, Tokai University, Kitakaname, Hiratsuka-shi, Kanagawa 259-1292, Japan. ishihara@tokai-u.jp.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Ishihara
authors.affiliation: Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India. kamit@barc.gov.in.
authors.forename: Amit
authors.initials: A
authors.lastname: Kunwar
authors.affiliation: Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India. kindira@barc.gov.in.
authors.forename: Kavirayani Indira
authors.initials: KI
authors.lastname: Priyadarsini
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D000976:Antipain / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism; D005227:Fatty Acids / Q000737:chemistry / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006573:Heterocyclic Compounds, 1-Ring / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008054:Lipid Peroxides / Q000737:chemistry / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D016566:Organoselenium Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase
chemical_list: C553726:3,4-dihydroxy-1-selenolane; D000975:Antioxidants; D005227:Fatty Acids; D006573:Heterocyclic Compounds, 1-Ring; D008054:Lipid Peroxides; D008081:Liposomes; D016566:Organoselenium Compounds; D000976:Antipain; D002784:Cholesterol; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase
keywords: TBARS; antioxidant; colony formation assay; lipid peroxidation