Isoxazole substituted chromans against oxidative stress-induced neuronal damage.
Identifieur interne : 001536 ( Main/Exploration ); précédent : 001535; suivant : 001537Isoxazole substituted chromans against oxidative stress-induced neuronal damage.
Auteurs : Maria Koufaki [Grèce] ; Alexandra Tsatsaroni ; Xanthippi Alexi ; Helène Guerrand ; Sofia Zerva ; Michael N. AlexisSource :
- Bioorganic & medicinal chemistry [ 1464-3391 ] ; 2011.
Descripteurs français
- KwdFr :
- Animaux, Catéchols (), Catéchols (pharmacologie), Catéchols (synthèse chimique), Chromanes (), Chromanes (pharmacologie), Chromanes (synthèse chimique), Hippocampe (), Hippocampe (cytologie), Humains, Isoxazoles (), Isoxazoles (pharmacologie), Isoxazoles (synthèse chimique), Mort cellulaire (), Neurones (), Neurones (physiologie), Neuroprotecteurs (), Neuroprotecteurs (pharmacologie), Neuroprotecteurs (synthèse chimique), Souris, Stress oxydatif (), Évaluation préclinique de médicament.
- MESH :
- cytologie : Hippocampe.
- pharmacologie : Catéchols, Chromanes, Isoxazoles, Neuroprotecteurs.
- physiologie : Neurones.
- synthèse chimique : Catéchols, Chromanes, Isoxazoles, Neuroprotecteurs.
- Animaux, Catéchols, Chromanes, Hippocampe, Humains, Isoxazoles, Mort cellulaire, Neurones, Neuroprotecteurs, Souris, Stress oxydatif, Évaluation préclinique de médicament.
English descriptors
- KwdEn :
- Animals, Catechols (chemical synthesis), Catechols (chemistry), Catechols (pharmacology), Cell Death (drug effects), Chromans (chemical synthesis), Chromans (chemistry), Chromans (pharmacology), Drug Evaluation, Preclinical, Hippocampus (cytology), Hippocampus (drug effects), Humans, Isoxazoles (chemical synthesis), Isoxazoles (chemistry), Isoxazoles (pharmacology), Mice, Neurons (drug effects), Neurons (physiology), Neuroprotective Agents (chemical synthesis), Neuroprotective Agents (chemistry), Neuroprotective Agents (pharmacology), Oxidative Stress (drug effects).
- MESH :
- chemical , chemical synthesis : Catechols, Chromans, Isoxazoles, Neuroprotective Agents.
- chemical , chemistry : Catechols, Chromans, Isoxazoles, Neuroprotective Agents.
- chemical , pharmacology : Catechols, Chromans, Isoxazoles, Neuroprotective Agents.
- cytology : Hippocampus.
- drug effects : Cell Death, Hippocampus, Neurons, Oxidative Stress.
- physiology : Neurons.
- Animals, Drug Evaluation, Preclinical, Humans, Mice.
Abstract
We have previously reported that catechol-bearing regioisomers of 5-isoxazolyl-6-hydroxy-chroman display higher in vitro neuroprotective activity, compared to hybrids with other nitrogen heterocycles, but their activity is hampered by cytotoxicity at higher concentrations. In an effort to discover non-cytotoxic isoxazole substituted chromans of high neuroprotective activity, 20 new 3- and 5-substituted (chroman-5-yl)-isoxazoles and (chroman-2-yl)-isoxazoles were synthesized using the copper(I)-catalysed cycloaddition reaction between in situ generated nitrile oxides and terminal acetylenes. An additional aim was to further explore the effect of the isoxazole ring substituents on the neuroprotective activity. The activity of these compounds against oxidative stress-induced death (oxytosis) of neuronal HT22 cells was evaluated and interesting SARs for this group of analogues were derived. The vast majority of new chroman analogues displayed high in vitro neuroprotective activity displaying EC(50) values below 1 μM and lacked cytotoxicity. The position of substituents on the isoxazole ring influences the activity of the regioisomers, with the 3-aryl-5-(chroman-5-yl)-isoxazoles, 17 and 18 and bis-chroman 20 displaying higher neuroprotective activity (EC(50)∼0.3 μM) compared to other (chroman-5-yl) and (chroman-2-yl)-isoxazoles.
DOI: 10.1016/j.bmc.2011.06.074
PubMed: 21778061
Affiliations:
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Le document en format XML
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Alexis</name></author></analytic><series><title level="j">Bioorganic & medicinal chemistry</title><idno type="eISSN">1464-3391</idno><imprint><date when="2011" type="published">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Catechols (chemical synthesis)</term><term>Catechols (chemistry)</term><term>Catechols (pharmacology)</term><term>Cell Death (drug effects)</term><term>Chromans (chemical synthesis)</term><term>Chromans (chemistry)</term><term>Chromans (pharmacology)</term><term>Drug Evaluation, Preclinical</term><term>Hippocampus (cytology)</term><term>Hippocampus (drug effects)</term><term>Humans</term><term>Isoxazoles (chemical synthesis)</term><term>Isoxazoles (chemistry)</term><term>Isoxazoles (pharmacology)</term><term>Mice</term><term>Neurons (drug effects)</term><term>Neurons (physiology)</term><term>Neuroprotective Agents (chemical synthesis)</term><term>Neuroprotective Agents (chemistry)</term><term>Neuroprotective Agents (pharmacology)</term><term>Oxidative Stress (drug effects)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Catéchols ()</term><term>Catéchols (pharmacologie)</term><term>Catéchols (synthèse chimique)</term><term>Chromanes ()</term><term>Chromanes (pharmacologie)</term><term>Chromanes (synthèse chimique)</term><term>Hippocampe ()</term><term>Hippocampe (cytologie)</term><term>Humains</term><term>Isoxazoles ()</term><term>Isoxazoles (pharmacologie)</term><term>Isoxazoles (synthèse chimique)</term><term>Mort cellulaire ()</term><term>Neurones ()</term><term>Neurones (physiologie)</term><term>Neuroprotecteurs ()</term><term>Neuroprotecteurs (pharmacologie)</term><term>Neuroprotecteurs (synthèse chimique)</term><term>Souris</term><term>Stress oxydatif ()</term><term>Évaluation préclinique de médicament</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Catechols</term><term>Chromans</term><term>Isoxazoles</term><term>Neuroprotective Agents</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Catechols</term><term>Chromans</term><term>Isoxazoles</term><term>Neuroprotective Agents</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Catechols</term><term>Chromans</term><term>Isoxazoles</term><term>Neuroprotective Agents</term></keywords><keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Hippocampe</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Hippocampus</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Death</term><term>Hippocampus</term><term>Neurons</term><term>Oxidative Stress</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Catéchols</term><term>Chromanes</term><term>Isoxazoles</term><term>Neuroprotecteurs</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Neurones</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Neurons</term></keywords><keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>Catéchols</term><term>Chromanes</term><term>Isoxazoles</term><term>Neuroprotecteurs</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Drug Evaluation, Preclinical</term><term>Humans</term><term>Mice</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Catéchols</term><term>Chromanes</term><term>Hippocampe</term><term>Humains</term><term>Isoxazoles</term><term>Mort cellulaire</term><term>Neurones</term><term>Neuroprotecteurs</term><term>Souris</term><term>Stress oxydatif</term><term>Évaluation préclinique de médicament</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We have previously reported that catechol-bearing regioisomers of 5-isoxazolyl-6-hydroxy-chroman display higher in vitro neuroprotective activity, compared to hybrids with other nitrogen heterocycles, but their activity is hampered by cytotoxicity at higher concentrations. In an effort to discover non-cytotoxic isoxazole substituted chromans of high neuroprotective activity, 20 new 3- and 5-substituted (chroman-5-yl)-isoxazoles and (chroman-2-yl)-isoxazoles were synthesized using the copper(I)-catalysed cycloaddition reaction between in situ generated nitrile oxides and terminal acetylenes. An additional aim was to further explore the effect of the isoxazole ring substituents on the neuroprotective activity. The activity of these compounds against oxidative stress-induced death (oxytosis) of neuronal HT22 cells was evaluated and interesting SARs for this group of analogues were derived. The vast majority of new chroman analogues displayed high in vitro neuroprotective activity displaying EC(50) values below 1 μM and lacked cytotoxicity. The position of substituents on the isoxazole ring influences the activity of the regioisomers, with the 3-aryl-5-(chroman-5-yl)-isoxazoles, 17 and 18 and bis-chroman 20 displaying higher neuroprotective activity (EC(50)∼0.3 μM) compared to other (chroman-5-yl) and (chroman-2-yl)-isoxazoles.</div></front></TEI><affiliations><list><country><li>Grèce</li></country><region><li>Attique (région)</li></region><settlement><li>Athènes</li></settlement></list><tree><noCountry><name sortKey="Alexi, Xanthippi" sort="Alexi, Xanthippi" uniqKey="Alexi X" first="Xanthippi" last="Alexi">Xanthippi Alexi</name><name sortKey="Alexis, Michael N" sort="Alexis, Michael N" uniqKey="Alexis M" first="Michael N" last="Alexis">Michael N. Alexis</name><name sortKey="Guerrand, Helene" sort="Guerrand, Helene" uniqKey="Guerrand H" first="Helène" last="Guerrand">Helène Guerrand</name><name sortKey="Tsatsaroni, Alexandra" sort="Tsatsaroni, Alexandra" uniqKey="Tsatsaroni A" first="Alexandra" last="Tsatsaroni">Alexandra Tsatsaroni</name><name sortKey="Zerva, Sofia" sort="Zerva, Sofia" uniqKey="Zerva S" first="Sofia" last="Zerva">Sofia Zerva</name></noCountry><country name="Grèce"><region name="Attique (région)"><name sortKey="Koufaki, Maria" sort="Koufaki, Maria" uniqKey="Koufaki M" first="Maria" last="Koufaki">Maria Koufaki</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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