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

Abstract

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