β-Carboline alkaloids bind DNA

beta-Carboline alkaloids present in Peganum harmala (harmal) have recently drawn attention due to their antitumor activities. The mechanistic studies indicate that beta-carboline derivatives inhibit DNA topoi-somerases and interfere with DNA synthesis. They interact with DNA via both groove binding and inter-calative modes and cause major DNA structural changes. The aim of this study was to examine the interactions of five beta-carboline alkaloids (harmine, harmane, harmaline, harmalol and tryptoline) with calf-thymus DNA in aqueous solution at physiological conditions, using constant DNA concentration (6.25 mM) and various alkaloids/polynucleotide (phosphate) ratios of 1/240, 1/160, 1/80, 1/40, 1/20, 1/10, 1/5, 1/2 and 1/1. Fourier transform infrared (FTIR) and UV-visible spectroscopic methods were used to determine the ligand binding modes, the binding constants, and the stability of alkaloids-DNA complexes in aqueous solution. Spectroscopic evidence showed major binding of alkaloids to DNA with overall binding constants of K-harmine - DNA = 3.44 x 10(7) M-1. K-harmane - DNA = 1.63 x 10(5) M-1, K-harmaline - DNA = 3.82 x 10(5) M-1, K-harmalol - DNA = 6.43 x 10(5) M-1 and K-tryptoline - DNA = 1.11 x 10(5) M-1. The affinity of alkaloids-DNA binding is in the order of harmine > harmalol > harmaline > harmane > tryptoline. No biopolymer secondary structural changes were observed upon alkaloid interaction and DNA remains in the B-family structure in these complexes. (C) 2010 Elsevier B.V. All rights reserved.