Design and synthesis of 1,2-dithiolane derivatives and evaluation of their neuroprotective activity

• Published in: Bioorganic & medicinal chemistry letters Vol. 17; no. 15; pp. 4223 - 4227
• Main Authors: Koufaki, Maria, Kiziridi, Christina, Nikoloudaki, Faidra, Alexis, Michael N.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-08-2007; Elsevier
• Subjects: Biological and medical sciences; Cell Line; Drug Evaluation, Preclinical; Heteroaromatic; Hippocampus - cytology; Hippocampus - drug effects; Lipoic acid; Medical sciences; Neurodegeneration; Neuropharmacology; Neuroprotective agent; Neuroprotective Agents - chemical synthesis; Neuroprotective Agents - pharmacology; Oxidative stress; Pharmacology. Drug treatments; Thioctic Acid - analogs & derivatives; Thioctic Acid - chemical synthesis; Thioctic Acid - chemistry; Thioctic Acid - pharmacology; Lipoic acid; Oxidative stress; Heteroaromatic; Neurodegeneration; Pyrocatechol derivatives; Tetrazole derivatives; Thiazole derivatives; Nervous system; Amides; Degeneration; Chemical synthesis; Nervous system diseases; Dopamine; Rodentia; Neuroprotective agent; Antioxidant; Catecholamine; Glutamate; In vitro; Biological activity; Vertebrata; Mammalia; Cell line; Neuron; Mouse; Animal; Biogenic amine; Triazole derivatives; Neurotransmitter; Phenols; Conjugated compound
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2007.05.036

We designed and synthesized new analogues containing 1,2-dithiolane-3-alkyl and protected or free catechol moieties connected through heteroaromatic rings such as triazole, 1,2,4-oxadiazole, 1,3,4-oxadiazole, tetrazole or thiazole in order to explore the influence of the bioisosteric replacement of the amide group on the neuroprotective activity of the lipoic acid/dopamine conjugate. Evaluation of the activity of the new compounds, using glutamate-challenged hippocampal HT22 cells, showed that incorporation of heteroaromatic rings in the alkyl-1,2-dithiolane moieties in conjunction with another antioxidant, in this case catechol, may result in strong neuroprotective activity.