New tetracyclic heteroaromatic compounds based on dehydroamino acids: photophysical and electrochemical studies of interaction with DNA

Abstract

A benzothienoindole (BTIN) and a benzofuroindole (BFIN) were synthesized in high yields, as potential new DNA target compounds, using a metal-assisted intramolecular CeN cyclization of the methyl esters of N-(tert-butoxycarbonyl)-b,b-bis(dibenzothien-4-yl or dibenzofur-4-yl)dehydroalanines. The latter were obtained by a bis-Suzuki coupling of a b,b-dibromodehydroalanine with the corresponding heteroarylboronic acids. The absorption and fluorescence properties of the new tetracyclic compounds were studied in different solvents and in the presence of salmon sperm DNA. The results in several solvents show that either BTIN or BFIN can be used as fluorescence solvent sensitive probes. Spectroscopic studies of their interaction with dsDNA allowed to determine binding constant (K i) values and binding site sizes (n). Fluorescence quenching experiments using iodide ion showed that intercalation is the preferred mode of binding to DNA. From the results obtained, BTIN is the more intercalative compound and has a higher affinity to DNA. The interaction of BTIN with DNA was also studied electrochemically, by using differential pulse voltammetry (DPV) in connection with disposable pencil graphite electrode (PGE). After the interaction of BTIN with DNA, the oxidation signals of BTIN and adenine strongly decreased. The latter result was attributed to the binding of BTIN to DNA and the former points to a possible damage of the oxidizable groups of BTIN after intercalation into DNA. The results of spectroscopic and electrochemical studies of BTIN interaction with DNA are in good agreement.

The Comparison of Electrochemical Assay and Agarose Gel Electrophoresis for the Determination of DNA Damage Induced by Kainic Acid

“…In similar to earlier studies [12,15,17,18,36,37] presenting electrochemical detection of DNA damage induced by several compounds/agents, or by g-radiation, a decrease at the magnitude of guanine signal was similarly observed in our study after in vitro and in vivo interaction of KA with ctdsDNA and genomic DNA in the solution phase. This decrease at the guanine signal can be attributed to the induction of oxidative DNA damage basically on guanine bases, that was also similarly explained for other DNA interactions [17,38].…”

“…The pretreated PGEs were immersed into the vials containing either 110 mL of samples containing DNA, or KA incubated DNA. The electrodes were then kept in these vials during 7.5 min followed by passive adsorption procedure [12,14,36]. The PGEs were washed with ABS for 10 s.…”

“…The interactions of some anticancer drugs with DNA have been studied by a variety of techniques [9,10] and in recent years, there is a growing interest in the electrochemical investigations of interactions between anticancer drugs and other DNA-targeted molecules and nucleic acids [11,12].…”

Interaction of antitumoral fluorescent heteroaromatic compounds, a benzothienopyrrole and two thienoindoles, with DNA and lipid membranes

“…Some of these compounds were shown to be DNA intercalators, using absorption and fluorescence techniques [18]. More recently, heteroaryl and heteroannulated indoles [16][17][18][19] and a benzothieno [3,2-b]pyrrole [17] were incorporated in lipid bilayers of phospholipid components of biological membranes (DPPC, DOPE and Egg-PC). Fluorescence anisotropy measurements indicated that they were located in the lipid bilayer, feeling the differences between the gel and the liquidcrystalline phases.…”

Studies on Interaction of Safranine T with Herring Sperm DNA in γ−Cyclodextrin

“…Organic dyes are stabilized on groove by binding and intercalation with DNA through a series of associative interactions such as hydrogen bond, attractive van der Waals, hydrophobic interaction and so on [3]. The intercalative binding is stronger than other two binding modes because the surface of intercalative molecule is inserted into base pairs of DNA.…”