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

WOS: 000372592900008PubMed ID: 26970662Oxidative 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 beta-induced damage was examined by MTT assay and their ability in reduction of ROS generation induced by amyloid beta 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 mu M. In conclusion, MLT derivatives represent promising scaffolds for discovery of effective antioxidant and neuroprotective agents. (C) 2016 Elsevier Ltd. All rights reserved.Scientific and Technological Research Council of Turkey (TUBITAK) Research and DevelopmentTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [109S099]; Shiraz University of Medical Sciences [94-01-12-10056]This work was supported by the Scientific and Technological Research Council of Turkey (TUBITAK) Research and Development Grant 109S099. The authors also wish to thank the financial support of the Vice-Chancellor for Research, Shiraz University of Medical Sciences (grant number: 94-01-12-10056). Authors would also like to thank Ege University, Faculty of Pharmacy, Pharmaceutical Sciences Research Center (FABAL) for providing laboratory facilities for ROS analysis