title: Synthesis of tropolone derivatives and evaluation of their in vitro neuroprotective activity.
abstract: beta-Thujaplicin (hinokitiol or 2-hydroxy-4-isopropyl-2,4,6-cycloheptatrien-1-one), a natural tropolone, shows numerous activities while its synthetic analogues were found to exhibit anticancer and anti-ischemic activity. However, the ability of tropolone derivatives to protect neuronal cells from oxidative stress-induced cell damage has not been studied so far. As an ongoing effort toward highly effective antioxidants with potential neuroprotective activity, we have synthesized 7-substituted derivatives of beta-thujaplicin and its methoxy analogue. The substituents were heterocycles (piperazine, morpholine) or heteroaromatics (triazoles, pyridine). Only the piperazine derivatives of beta-thujaplicin were able to protect HT22 hippocampal neurons from oxidative stress-induced cell death.
authors.affiliation: Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, 48 Vas Constantinou Ave, 116 35 Athens, Greece. mkoufa@eie.gr
authors.forename: Maria
authors.initials: M
authors.lastname: Koufaki
authors.forename: Elissavet
authors.initials: E
authors.lastname: Theodorou
authors.forename: Xanthippi
authors.initials: X
authors.lastname: Alexi
authors.forename: Faidra
authors.initials: F
authors.lastname: Nikoloudaki
authors.forename: Michael N
authors.initials: MN
authors.lastname: Alexis
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016923:Cell Death; D002460:Cell Line; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D015394:Molecular Structure; D039821:Monoterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000494:pharmacology; D014334:Tropolone / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D039821:Monoterpenes; D018696:Neuroprotective Agents; D014334:Tropolone; C009479:beta-thujaplicin