AChE inhibitory effect, anti-oxidant and anti-inflammatory properties of cyclen and L-Dopa related compounds: Targeting in neurodegenerative disease

Abstract

1,4,7,10-tetraazacyclododecane (cyclen), a macrocyclic polyamine, and L-3,4-dihydroxyphenylalanine (L-DOPA), a tyrosine polyphenolic compound are compounds having various applications in medicine, biology, chemistry, etc. Derivatization of these precursor compounds aims to increase their biological activity, blood-brain barrier (BBB) permeability, solubility, binding ability, and lower toxicity. Synthesis and in vitro cytotox-icity of small new peptide-modified cyclen and L-DOPA derivatives were described previously. In the present study, in vitro biological activities such as radical scavenging capacity, anti-inflammatory, and acetylcholines-terase (AChE) inhibitory activities of compounds were evaluated. The results showed that some of them are good candidates for further detailed studies targeting neurodegenerative diseases, such as Alzheimer's and Parkin-son's, and their pharmacokinetics and interaction with amyloidal aggregations characterized for neurodegen-erative diseases. Dopa-DH-Dopa showed the highest anti-oxidant activity (IC50, 0.12 mu M) and Dopa-HH-Dopa as AChE inhibitor (21 mu M). Dopa-HH mainly inhibited nitric oxide (NO) production as an inflammatory marker.