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

Autor: Hande Gurer-Orhan, Omidreza Firuzi, Senem Ozcan, Cigdem Karaaslan, Marjan Tavakkoli, Sibel Suzen, Luciano Saso
Rok vydání: 2016
Předmět:
0301 basic medicine
Antioxidant
Indoles
medicine.medical_treatment
Clinical Biochemistry
antioxidant activity
Pharmaceutical Science
medicine.disease_cause
Biochemistry
PC12 Cells
Antioxidants
0302 clinical medicine
Drug Discovery
Cytotoxicity
Melatonin
chemistry.chemical_classification
Molecular Structure
Chemistry
3. Good health
Neuroprotective Agents
030220 oncology & carcinogenesis
alzheimer's disease
Molecular Medicine
medicine.drug
Cell Survival
CHO Cells
Neuroprotection
03 medical and health sciences
Structure-Activity Relationship
Cricetulus
medicine
Animals
Humans
MTT assay
Molecular Biology
Indole test
Reactive oxygen species
Amyloid beta-Peptides
Dose-Response Relationship
Drug
Organic Chemistry
Peptide Fragments
Rats
amyloid beta
indole
melatonin
030104 developmental biology
Reactive Oxygen Species
Oxidative stress
Zdroj: Bioorganicmedicinal chemistry. 24(8)
ISSN: 1464-3391
Popis: 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.
Databáze: OpenAIRE
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