Synthesis of quinoline/naphthalene-containing azaphenothiazines and their potent in vitro antioxidant properties.
New tetracyclic and pentacyclic azaphenothiazines containing one or two quinoline rings instead of benzene rings were obtained in the original reactions of isomeric diquinodithiins, dichlorodiquinolinyl sulfides, and disulfide with aromatic amines. The type of ring fusion in the azaphenothiazine system was concluded from the1H NMR spectra. The obtained azaphenothiazines were evaluated in vitro for their antioxidant activity on rat hepatic microsomal membranes for protection of non-enzymatic lipid peroxidation promoted by the Fe2+/ascorbic acid redox system. Most compounds exhibited a very significant antioxidant activity with IC50values between 1 and 23 μM. The degree of antioxidant activity depends on the lipophilicity and molecular size as well as the (non)substitution of the thiazine nitrogen atom and type of ring system fusion. It is the first time to our knowledge that azaphenothiazines are shown to exhibit such potent antioxidant activity.
Department of Organic Chemistry, School of Pharmacy with the Division of Laboratory Medicine, The Medical University of Silesia, Jagiellońska 4, 41-200 Sosnowiec, Poland.
Małgorzata
M
Jeleń
Department of Medicinal Chemistry, Faculty of Pharmacy, University of Athens, 15771 Athens, Greece.
Eugenia I
EI
Bavavea
Department of Medicinal Chemistry, Faculty of Pharmacy, University of Athens, 15771 Athens, Greece.
Maria
M
Pappa
Department of Medicinal Chemistry, Faculty of Pharmacy, University of Athens, 15771 Athens, Greece.
Angeliki P
AP
Kourounakis
Department of Organic Chemistry, School of Pharmacy with the Division of Laboratory Medicine, The Medical University of Silesia, Jagiellońska 4, 41-200 Sosnowiec, Poland.
Beata
B
Morak-Młodawska
Department of Organic Chemistry, School of Pharmacy with the Division of Laboratory Medicine, The Medical University of Silesia, Jagiellońska 4, 41-200 Sosnowiec, Poland.
Krystian
K
Pluta
Diquinothiazines; Lipid peroxidation; Lipophilicity; NH-azaphenothiazines; Phenothiazine derivatives; Quinonaphthothiazines