Invited feature articleLuminescent characterization of interaction efficiency between (−)-cytisine and amino acids an indicator of anti-inflammatory of some 12-N-substituted (−)-cytisine derivatives

- The spectral fluorescent properties of some 12-N-substituted (−)cytisine have been studied and their relative quantum yields and lifetimes in the electronically excited states have been defined.
- The quenching of fluorescence of Tyr and Trp by amino-derivatives of 12-N-methyl cytosine as well as the FL quenching of cytosines themselves by Ser and Arg was studied.
- The static mechanism of the quenching of aromatic amino acids and dynamic mechanism for the fluorescence quenching of cytisines by Arg due to the reversible photo-induced electron transfer occurs.
- The thermodynamic assessment of the photo-induced electron transfer probability according to the Weller equation agrees with the observed regularities and series of bioactivity of the cytisines.
- The 3-amino-derivatives of 12-N-methylcytisine are able to interact with aromatic amino acids resulting in the ligand-protein complexation. Formation of such complexes may influence on biological functions of the enzyme in general.

In the present work, the spectral fluorescent properties of N-R-12-N-methylcytisine-3-amines (R = 2-furylmethyl, 2-hydroxybenzyl, 2-thienylmethyl and 2-phenylprop-2-en-1-yl) have been studied and their relative quantum yields and lifetimes in the electronically excited states have been defined. These compounds have bioactivity as potential inhibitors of cyclooxygenase-2 (COX-2). We have studied the quenching of fluorescence (FL) of L-tyrosine (Tyr) and L-tryptophan (Trp) by amino-derivatives of 12-N-methylcytisine as well as the FL quenching of cytisines themselves by L-serine (Ser) and L-arginine (Arg). The found Stern-Volmer constants and lifetimes of the excited states reveal static mechanism of the quenching of aromatic amino acids and dynamic mechanism for the FL quenching of cytisines by Arg (Ser does not quench FL) due to the reversible photo-induced electron transfer (PET). The thermodynamic assessment of the PET probability according to the Weller equation agrees with the observed regularities and series of bioactivity of the cytisines. Using molecular docking, we have found the most probable positions of the 12-N-methylcytisine derivatives in the active site of COX-2 where their stacking interactions with Trp387 and Tyr385 and hydrogen bonding with Arg120 and Ser530 occur. As the mentioned amino acids play a key role in the complexion of the studied compounds by COX-2, we have proposed that bioactivity mechanism of the lead compounds implies the COX-2 inhibition by the withdrawal of electron from electron-transfer processes in the chain HEM-His388-Trp387-His386-Tyr385 resulted from their stacking interactions with Trp and/or Tyr.

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