Generation of Free Radicals by Emodic Acid and its [d-Lys6]GnRH-conjugate¶
| Autor: | Frédérique Barbosa, Georg Gescheidt, Izhak Bilkis, Yehuda Mazur, Vincent Péron, Mati Fridkin, Yitzhak Koch, Shai Rahimipour, Lev Weiner |
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| Rok vydání: | 2007 |
| Předmět: |
Emodin
Free Radicals Photochemistry Radical Antineoplastic Agents Gonadotropin-releasing hormone Biochemistry Gonadotropin-Releasing Hormone chemistry.chemical_compound Neoplasms Moiety Humans Physical and Theoretical Chemistry chemistry.chemical_classification Reactive oxygen species Photosensitizing Agents Spin trapping Superoxide General Medicine Combinatorial chemistry Amino acid chemistry Photochemotherapy Receptors LHRH |
| Zdroj: | Photochemistry and Photobiology. 74:226-236 |
| ISSN: | 0031-8655 |
| DOI: | 10.1562/0031-8655(2001)0740226gofrbe2.0.co2 |
| Popis: | In an attempt to develop an efficient chemotherapeutic agent targeted at malignant cells that express receptors to gonadotropin releasing hormone (GnRH) we coupled [D-Lys6]GnRH covalently to an emodin derivative, i.e. emodic acid (Emo) to yield [D-Lys6(Emo)]GnRH. Emodin is a naturally occurring anthraquinone which is widely used as a laxative and has other versatile biological activities. Physico-chemical studies employing electron paramagnetic resonance and electrochemistry of the conjugate as well as the (Emo) moiety showed that these compounds could be easily reduced either chemically, photochemically or enzymatically to their corresponding semiquinones. In the presence of oxygen the semiquinones generated reactive oxygen species (ROS), mainly superoxide and hydroxyl radicals, which were detected by the spin trapping method. Moreover, upon irradiation with visible light these compounds produced ROS and a highly reactive excited triplet state of Emo, which by itself may cause the oxidation of certain electron acceptors such as amino acids and bases of nucleic acids. Thus, [D-Lys6]GnRH-photosensitizer conjugates may be potentially used for targeted photodynamic chemotherapy aimed at treating cancer cells that carry GnRH receptors. These conjugates may also induce cytotoxicity in the dark similar to common conventional chemotherapeutic agents. The peptidic moiety, [D-Lys6]GnRH, was found to be stable toward highly reactive ROS generated either from enzymatic reduction or upon photoirradiation. The physico-chemical properties of Emo were only marginally influenced by the peptidic [D-Lys6]GnRH carrier. |
| Databáze: | OpenAIRE |
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