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

• Peptide-modified cyclen and L-DOPA derivatives were synthesized. • In vitro anti-inflammatory, ORAC, and AChE inhibitory activities were evaluated. • The effectiveness of compounds against Alzheimer's diseases was confirmed. 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 cytotoxicity 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 acetylcholinesterase (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 Parkinson's, and their pharmacokinetics and interaction with amyloidal aggregations characterized for neurodegenerative diseases. Dopa-DH-Dopa showed the highest anti-oxidant activity (IC 50 , 0.12 µM) and Dopa-HH-Dopa as AChE inhibitor (21 µM). Dopa-HH mainly inhibited nitric oxide (NO) production as an inflammatory marker. [Display omitted] [ABSTRACT FROM AUTHOR]