Publication: Çeşitli kumarin türlerinin oksidatif stres üzerine etkisi
Abstract
ÇEŞİTLİ KUMARİN TÜRLERİNİN OKSİDATİF STRES ÜZERİNE ETKİSİ Oksijenin, dünyadaki karmaşık hayatın oluşumunda çok önemli merkezi bir rolü vardır. Çünkü oksijenik fotosentez ve oksijenli solunum sayesinde gezegenimizin biyosferinde hayatın canlılığını sağlar. Oksijen aynı zamanda reaktif oksijen türleri (ROS) diye adlandırılan toksik molekülleri de oluşturabilir. Çeşitli biyotik ve abiyotik faktörler oldukça reaktif ve toksik olan, proteinlere, lipitlere, karbonhidratlara ve DNA'ya hasar veren ve oksidatif strese neden olan reaktif oksijen türlerinin oluşumuna sebep olur. ROS’lar hem süperoksit (O2•−), hidroksil (OH•), perhidroksil (HO2•) gibi serbest radikalleri hem de hidrojen peroksit (H2O2), singlet oksijen (1O2) gibi radikal olmayan moleküllerden meydana gelirler. Antioksidan savunma sistemleri ise organizmayı oksidatif strese karşı korurlar. Kumarinler doğada özel bir role sahip, önemli bir bileşik grubunu oluştururlar. Kumarin ve onların türevleri sergiledikleri antioksidan, antitrombotik, antinflamatuvar, anti-HIV, antihelmintik gibi farmakolojik özelliklerinden dolayı günden güne popülerliklerini arttırmaktadırlar. Tüm bu özelliklerinden dolayı kumarin ve türevleri kapsamlı araştırmalara tabi tutulmuşlardır. Bu tez çalışmasında Organik Kimya ve Biyokimya tarafından sentezlenen kumarinlerin antioksidan fonksiyonları hakkında bilgi edinmek amacıyla, kumarinlerin antioksidan aktiviteleri DPPH Üzerinden Serbest Radikal Süpürücü Etki Tayini (DPPH), CUPRAC (Cu2+ indirgeyici antioksidan kapasite) Yöntemi, FRAP (Fe 3+ indirgeyici antioksidan kapasite) Yöntemi gibi metotlarla saptanmıştır. Denemelerin sonuçları incelendiğinde kumarin türevlerinin antioksidan özelliklerinın iskelet yapılarına göre değişkenlik gösterdiği, yapısında en fazla -OH grubu içeren VIII numaralı kumarinin (6,7-Dihidroksi-4-(3,4-dihidroksifenil)kumarin) en yüksek antioksidan aktiviteye sahip olduğu; yapılarında -OH, -OCH3, -OCOCH3 gibi substitüye grup içermeyen V ve VI numaralı kumarinlerin (srasıyla 7,8-Benzo-3-bifenilkumarin; 6,7-Benzo-3-bifenilkumarin) en düşük antioksidan aktiviteye sahip oldukları saptanmıştır.
INVESTIGATION of NOVEL SYNTHESIZED COUMARINS on OXIDATIVE STRESS Oxygen has a central role in the evolution of complex life on earth mainly because of the biochemical symmetry of oxygenic photosynthesis and aerobic respiration that can maintain homeostasis within our planet biosphere. Oxygen can also produce toxic molecules, reactive oxygen species (ROS). Various biotic and abiotic factors lead to the overproduction of reactive oxygen species (ROS) in organism which are highly reactive and toxic and cause damage to proteins, lipids, carbohydrates and DNA which ultimately results in oxidative stress. The ROS comprises both free radical (O2•−, superoxide radicals; OH•, hydroxyl radical; HO2•, perhydroxy radical and RO•, alkoxy radicals) and non-radical (molecular) forms (H2O2,hydrogen peroxide and 1O2, singlet oxygen). The antioxidant defense machinery protects organism against oxidative stress damages. Coumarins form an elite class of compounds, which occupy a special role in nature. Coumarins and their derivatives have been found to exhibit a variety of biological and pharmacological activities and have raised considerable interest because of their potential beneficial effects on human health. They have been reported to posses among others: anti-HIV, anticoagulant, antibacterial anticancer, anthelmintic, anti-inflammatory and antioxidant activities. As a result, coumarins and their derivatives have been the subject of extensive investigations. In this study in order to supply new information on the antioxidant functions of coumarins which were synthesized in our Organic Chemistry and Biochemistry laboratories, antioxidant activities of coumarins were evaluated using ferric reducing antioxidant power (FRAP), (Cupric Reducing Antioxidant Capacity (Cuprac), 1,1-Diphenyl-2-picrylhydrazyl (DPPH) Radical Scavenging assays respectively. Our results showed that coumarins containing more –OH groups in their skeleton like coumarin VIII (6,7-Dihydroxy-4-(3,4-dihidroxyphenyl)coumarin) displayed highest antioxidant activity while coumarins not containing -OH, -OCH3 , -OCOCH3 functional groups like coumarin V (7,8-Benzo-3-biphenylcoumarin) and coumarin VI (6,7-Benzo-3-biphenylcoumarin) displayed low antioxidant activity.
INVESTIGATION of NOVEL SYNTHESIZED COUMARINS on OXIDATIVE STRESS Oxygen has a central role in the evolution of complex life on earth mainly because of the biochemical symmetry of oxygenic photosynthesis and aerobic respiration that can maintain homeostasis within our planet biosphere. Oxygen can also produce toxic molecules, reactive oxygen species (ROS). Various biotic and abiotic factors lead to the overproduction of reactive oxygen species (ROS) in organism which are highly reactive and toxic and cause damage to proteins, lipids, carbohydrates and DNA which ultimately results in oxidative stress. The ROS comprises both free radical (O2•−, superoxide radicals; OH•, hydroxyl radical; HO2•, perhydroxy radical and RO•, alkoxy radicals) and non-radical (molecular) forms (H2O2,hydrogen peroxide and 1O2, singlet oxygen). The antioxidant defense machinery protects organism against oxidative stress damages. Coumarins form an elite class of compounds, which occupy a special role in nature. Coumarins and their derivatives have been found to exhibit a variety of biological and pharmacological activities and have raised considerable interest because of their potential beneficial effects on human health. They have been reported to posses among others: anti-HIV, anticoagulant, antibacterial anticancer, anthelmintic, anti-inflammatory and antioxidant activities. As a result, coumarins and their derivatives have been the subject of extensive investigations. In this study in order to supply new information on the antioxidant functions of coumarins which were synthesized in our Organic Chemistry and Biochemistry laboratories, antioxidant activities of coumarins were evaluated using ferric reducing antioxidant power (FRAP), (Cupric Reducing Antioxidant Capacity (Cuprac), 1,1-Diphenyl-2-picrylhydrazyl (DPPH) Radical Scavenging assays respectively. Our results showed that coumarins containing more –OH groups in their skeleton like coumarin VIII (6,7-Dihydroxy-4-(3,4-dihidroxyphenyl)coumarin) displayed highest antioxidant activity while coumarins not containing -OH, -OCH3 , -OCOCH3 functional groups like coumarin V (7,8-Benzo-3-biphenylcoumarin) and coumarin VI (6,7-Benzo-3-biphenylcoumarin) displayed low antioxidant activity.