Effects of the Interaction Between β‐Carboline‐3‐carboxylic acid N‐Methylamide and Polynucleotides on Singlet Oxygen Quantum Yield and DNA Oxidative Damage

Abstract

The complexation of beta-carboline-3-carboxylic acid N-methylamide (betaCMAM) with the sodium salts of the nucleotides polyadenylic (Poly A), polycytidylic (Poly C), polyguanylic (Poly G), polythymidylic (Poly T) and polyuridylic (Poly U) acids, and with double stranded (dsDNA) and single stranded deoxyribonucleic acids (ssDNA) was studied at pH 4, 6 and 9. Predominant 1:1 complex formation is indicated from Job plots. Association constants were determined using the Benesi-Hildebrand equation. BetaCMAM-sensitized singlet oxygen quantum yields were determined at pH 4, 6 and 9, and the effects on this of adding oligonucleotides, dsDNA and ssDNA were studied at the three pH values. With dsDNA, the effect on betaCMAM triplet state formation was also determined through triplet-triplet transient absorption spectra. To evaluate possible oxidative damage of DNA following singlet oxygen betaCMAM photosensitization, we used thiobarbituric acid-reactivity assays and electrophoretic separation of DNA assays. The results showed no oxidative damage at the level of DNA degradation or strand break.

Photosensitized cleavage of plasmidic DNA by norharmane, a naturally occurring β-carboline

“…On the contrary, the experimental rate of DNA relaxation observed at pH 10.2 was much smaller than the corresponding rate at pH 4.7. On the other hand, in a very recent study 56 García-Zubiri et al have proven for another bC derivative that as a result of its complexation with DNA, the intersystem crossing process became less efficient, decreasing the amount of 1 O 2 generated by photosesitization. 72 On these facts, the photosensitizing properties of norharmane would involve other routes apart from the 1 O 2 attack to DNA.…”

“…Although the photophysics 32-53 and the photochemistry 54,55 of bCs have been extensively studied over the past two decades, only a few studies regarding the photosensitizing properties of these alkaloids have been described. 56,57 In the context of our studies to elucidate the mechanisms involved in the processes photosensitized by bCs, we describe here the first in vitro study of the photosensitized cleavage of plasmid DNA by norharmane upon UV-A irradiation, in both acidic and alkaline aqueous solutions as well as in physiological conditions. Norharmane is a good model compound for aromatic bCs in general due to its chemical structure (see Fig.…”

Interaction of a potential chloride channel blocker with a model transport protein: a spectroscopic and molecular docking investigation

“…The time-dependent decay of fluorescence anisotropy is a sensitive tool for gathering information about the rotational motion and rotational relaxation of the fluorophore embedded within an organized assembly. 4,14,38,39 The typical anisotropy decay profiles of the drug in the aqueous buffer as well as in the protein environment are presented in Fig. 6.…”

Photosensitized electron transfer within a self-assembled norharmane–2′-deoxyadenosine 5′-monophosphate (dAMP) complex

“…Although the interaction between several βC derivatives and nucleotides has been described, 21,41,42 it is noteworthy that these studies have been performed in solvents and pH conditions rather different from those used in the present work. We examined first the pH-dependence of the norharmane-dAMP interaction by UV-vis absorption, 1 H-NMR and fluorescence spectroscopy.…”

“…[18][19][20] Although this, only a few studies regarding the photosensitizing properties of these alkaloids have been described. 21,22 Recently, we have demonstrated that, upon UV-A irradiation, βCs derived from 9H-pyrido [3,4-b]indole or norharmane (Scheme 1) are able to induce DNA photodamage. 23,24 It has been shown that the interaction of βCs with DNA as well as the DNA photodamage strongly depend on the pH of the solution.…”