Background and Objectives: Neurodegenerative diseases and inflammation are
always linked to each other; therefore the elaboration of new chemical compounds, which
interact with pharmacological targets involved into these two processes, can become one of
ways of correction of these types of human CNS pathology. In the field of this problem the
anti-inflammatory activity of ten 3-amino derivatives of quinolizidine alkaloid (-)-cytisine
(the data about nootropic activity of these compounds are outlined by us previously) was
studied by using in vivo, in vitro and in silico approaches.
Methods: The anti-inflammatory activity of novel compounds was investigated on carrageenan-
induced model of inflammation in Rat paw following an established protocol.
COX-1 (ovin) and COX-2 (human recombinant) inhibition activities of tested compounds
assessed using a COX Fluorescent Inhibitor Screening Assay Kit. And as part of an in silico
screening the leading compounds were docked into the tyrosine sites of COX-1/COX-2 enzymes
(PDB code: 1DIY and 1CVU).
Results: It was established that ability of 3-(2-hydroxyphenyl)amino, 3-(4-hydroxyphenyl)
amino and 3-(3-phenylprop-2-en-1-yl)amino derivatives of 12-N-metylcytisine to inhibit the
carrageenan-induced paw oedema in rats is comparable with reference drug diclofenac. The
results of in vitro COX-1/COX-2 inhibition assay showed no significant activity of tested
compounds, except compounds with 2-hydroxyphenyl, 3-phenylprop-2-en-1-yl, furyl and
thiophenyl fragments which slightly reduce the activity of COX-2.
Conclusion: The tendency to occurrence of anti-inflammatory properties of synthesized derivatives
of quinolizidine alkaloid (-)-cytisine can be explained on the basis of molecular
docking results, which assume the possibility of interaction of more potent compounds with
key amino acids of COX-1/COX-2 active sites.