Interaction of Bioactive Pyrazolo[4,3-a]acridines with Human Serum Albumin

Abstract

<em>Several </em><em>heterocyclic bioactive fluorescent </em><em>3-alkyl-</em><em>3</em><em>H</em><em>-pyrazolo[4,3-</em><em>a</em><em>]acridin-11-carbonitriles were </em><em>conveniently </em><em>synthesized </em><em>from the reaction of 1-alkyl-1H-indazoles with different aryl acetonitrile in basic methanol solution in good yields. The interactions of </em><em>3</em><em>H</em><em>-pyrazolo[4,3-</em><em>a</em><em>]acridin-11-carbonitriles</em><em> with Human Serum Albumin (HSA) were studied by fluorescence spectroscopy. The binding of 3-alkyl-</em><em>3</em><em>H</em><em>-pyrazolo[4,3-</em><em>a</em><em>]acridin-11-carbonitriles</em><em> quenches the HSA </em><em>fluorescence, revealing a 1:1 interaction with a binding constant of about 1.28 × 10³ – 1.85 × 10³ M^-1.</em>A decrease in fluorescence intensity at 339 nm, when excited at 295 nm, is attributed to changes in<em> the environment of the protein fluorophores caused by the presence of the ligand. The results show </em><em>that pyrazolo[4,3-a]acridines with R=propyl, butyl, isobutyl and R'=chlorine substituents have suitable thermodynamic and binding parameters with HSA.</em><br />