Interaction of β-Carbolines with DNA: Spectroscopic Studies, Correlation with Biological Activity and Molecular Docking

Abstract

Quantitative interaction of twelve β-carboline derivatives with calf thymus deoxyribonucleic acid (ctDNA) using spectroscopic techniques was evaluated. The values of the binding constants (K b ) obtained for the complexes formed with the ctDNA ranged from 3.30 × 10 2 to 1.82 × 10 6 mol L −1 , being the β-carbolines with the N,N-dimethylaminophenyl group at position 1 the ones which presented the highest K b values. The binding mode between the β-carbolines evaluated and ctDNA was proposed from the KI assay, competition with ethidium bromide, and DNA thermal denaturation profile (T m ), where it was possible to infer that the evaluated alkaloids interact with ctDNA preferably via intercalation. Additionally, the correlation of K b values obtained with the IC 50 of seven human cancer cell lines was carried out. From this study, it was possible to observe a linear relation among most of the evaluated derivatives, obtaining r 2 values from 0.5360 to 0.9600. In addition, in silico molecular docking was performed to corroborate the experimental results.

Streptomyces nigra sp. nov. Is a Novel Actinobacterium Isolated From Mangrove Soil and Exerts a Potent Antitumor Activity in Vitro

“…Previous studies reported that β-carboline and a series of its derivatives (including harman alkaloids) inhibit DNA topoisomerases and interfere with DNA synthesis; They interact with DNA by groove binding and intercalation, which may lead to major structural changes in the DNA ( Nafisi et al, 2010 ). Further, they exert a pronounced antitumor activity against human tumor cells, including KB, DLD, NCI-H661, Hepa, and HepG2/A2 cell lines ( Prinsep et al, 1991 ; Shen et al, 2011 ; Silva et al, 2016 ). Glycodeoxycholic acid and taurodeoxycholic acid are important components of bile acid, and cause liver injury during cholestasis by inducing hepatocyte apoptosis via Fas-dependent and -independent mechanisms ( Higuchi et al, 2001 ).…”

Highly functionalized piperidines: Free radical scavenging, anticancer activity, DNA interaction and correlation with biological activity

“…The results are in agreement with same works in the literature that evaluated the correlation between interaction with DNA (K b ) and values of biological activity. Silva et al [24] obtained a linear relation from logK b between ctDNA and β-carboline derivatives with IC 50 values (μM) for six human tumor cell lineages, with determination coefficients (r 2 ) from 0.5360 to 0.9600. In a similar evaluation, da Silva et al [57] observed a linear relation from logK b between ctDNA and Schiff bases with GI 50 values (μg·mL −1 ) for seven human tumor cell lines, with correlation coefficients (r) from −0.9778 to +0.8693.…”

“…Computational methodologies, such as molecular docking, have been employed to providing new scaffolds with high potency and good tolerance [23] . After molecular dynamic completion, the optimized ct-DNA structure with the lowest RMSD value was used in this study [24] . Molecular docking was performed in tentative to observe some aspects in the formation of complexes, such as nitrogenous bases involvement, binding mode, type of interaction, and best conformation.…”

“…Molecular docking was performed in tentative to observe some aspects in the formation of complexes, such as nitrogenous bases involvement, binding mode, type of interaction, and best conformation. All methods were performed as described by Silva et al [24] .…”

Synthesis and In Vitro Antitumor Activity of Novel Bivalent β-Carboline-3-carboxylic Acid Derivatives with DNA as a Potential Target

“…The binding affinity of β -carboline derivatives ( 4B , 6i , 4D , and 6u ) to DNA were investigated through thermal denaturation experiments. Small molecules interact with DNA through the intercalation mode, which makes the DNA double helix more stable, thereby increasing the melting temperature ( T m ) [ 44 ]. Therefore, the thermal denaturation experiment provides a simple and effective method for detecting DNA-binding affinity.…”