2. Academic Validation
  3. Novel indole-based melatonin analogues: Evaluation of antioxidant activity and protective effect against amyloid β-induced damage

Novel indole-based melatonin analogues: Evaluation of antioxidant activity and protective effect against amyloid β-induced damage

  • Bioorg Med Chem. 2016 Apr 15;24(8):1658-64. doi: 10.1016/j.bmc.2016.02.039.
Hande Gurer-Orhan 1,  Cigdem Karaaslan 2,  Senem Ozcan 1,  Omidreza Firuzi 3,  Marjan Tavakkoli 3,  Luciano Saso 4,  Sibel Suzen 5
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Ege University, 35100 Izmir, Turkey.
  • 2 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, Tandogan 06100, Ankara, Turkey.
  • 3 Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
  • 4 Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, P. le Aldo Moro 5, 00185 Rome, Italy.
  • 5 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, Tandogan 06100, Ankara, Turkey. Electronic address: sibel@pharmacy.ankara.edu.tr.
PMID: 26970662 DOI: 10.1016/j.bmc.2016.02.039
Abstract

Oxidative stress has been recognized as a contributing factor in ageing and various diseases including Cancer and neuropathological disorders. Indole derivatives such as the neurohormone melatonin (MLT) constitute an important class of therapeutic agent in medicinal chemistry. MLT can scavenge different Reactive Oxygen Species and can also stimulate the synthesis of antioxidant Enzymes. As a part of our ongoing studies, a series of new indole-based hydrazide/hydrazone derivatives were synthesized as MLT analogues. Their antioxidant activity was investigated in human erythrocytes by evaluating their reducing effect against oxidation of a redox-sensitive fluorescent probe. Possible inherent cytotoxicity of the compounds was investigated in CHO-K1 cells by Lactate Dehydrogenase leakage test. Protection of neuronal PC12 cells against amyloid β-induced damage was examined by MTT assay and their ability in reduction of ROS generation induced by amyloid β was tested. MLT analogues having an o-halogenated aromatic moiety exhibited effective antioxidant properties without having any membrane-damaging effect. Moreover, derivatives having o-halogenated and dihalogenated aromatic side chain significantly protected neuronal cells at concentrations of 10 and 100 μM. In conclusion, MLT derivatives represent promising scaffolds for discovery of effective antioxidant and neuroprotective agents.

Keywords

Alzheimer’s disease; Amyloid β; Antioxidant activity; Indole; Melatonin.

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