Selective High Binding Affinity of Azacyanines to polyd(A) polyd(T)⋅polyd(T) Triplex: The Effect of Chain Length and Branching on Stabilization, Selectivity and Affinity

Tütüncü, Serra; Guloglu, Sercan; Kucukakdag, Ayca; Çetinkol, Özgül Persil

doi:10.1002/slct.201802802

Cited by 2 publications

(3 citation statements)

References 37 publications

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“…Accordingly, during the last years, the major focus of our research group has been the investigation of the interactions of azacyanines with different nucleic acid structures. ,,, Among the azacyanines investigated, only 2 of them named azacyanine4 (Aza4) and azacyanine5 (Aza5) were benzothiazole derivatives, and both of them were found to be binding to the human telomeric sequence tel24 and poly(A) with high affinity. , They were also recently evaluated for their potential as topoisomerase II inhibitors . However, one downside of the azacyanine synthesis via the previously reported method was the low yields.…”

Section: Introductionmentioning

confidence: 99%

Novel Fluorescent Azacyanine Compounds: Improved Synthesis and Optical Properties

et al. 2020

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Benzothiazoles are known to possess a number of biological activities and therefore are considered to be an important scaffold in the design and synthesis of pharmacophores. In this study, an improved synthesis method for novel fluorescent benzothiazole-based cyclic azacyanine (CAC) dyes bearing different electron-donating/withdrawing groups on their scaffold is presented. The improved method enabled us to increase the synthesis yield for the previously reported CACs. More importantly, it allowed us to synthesize new CAC dyes that were not synthesizable with the previously reported method. The synthesized dyes were characterized by 1 H and 13 C NMR spectroscopy, elemental analysis, and mass spectrometry and their optical (absorption and fluorescence) properties were investigated. All of the synthesized CACs were found to be displaying strong absorption within the range of 387–407 nm. The spectral shifts observed in the absorption and fluorescence measurements suggested that the spectroscopic and optical properties of CACs can be directly modulated by the nature of the electron-donating/withdrawing substituents. The fluorescence quantum yields (QYs) of the unsubstituted (parent CAC) and substituted CACs were also measured and compared. The fluorescence QY of CACs with electron-donating substituents (methoxy or ethoxy) was found to be at least four times higher than that of the parent CAC with no substitutions.

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Section: Introductionmentioning

confidence: 99%

Novel Fluorescent Azacyanine Compounds: Improved Synthesis and Optical Properties

et al. 2020

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“…The interactions of azacyanines with tel24 were first investigated using UV-Vis and circular dichroism (CD) spectroscopy in order to quickly survey and confirm the presence of interactions between the azacyanines and tel24. Such a survey also reveals changes in the secondary structure of tel24 upon azacyanine binding and the effect of azacyanine structure on tel24 binding [25,[28][29][30][31][32][33][34][35][36][37]. Our previous structural studies using NMR have shown that one azamethyl was binding to one tel24 G-quadruplex structure between the top quartet and the A-T base pairing in the loop region.…”

Section: Determination Of Binding Using Uv-vis and CD Spectroscopymentioning

confidence: 92%

“…Based on all these reported studies and our knowledge on azamethyl, we were inspired to explore a series of azacyanine compounds as potential G-quadruplex stabilizing compounds with the hope of finding a better candidate than azamethyl and understanding the effect of molecular structure on molecular recognition. In the present study, we evaluated the interactions of benzimidazole derivatives, differing from azamethyl in alkyl chain length and branching, with tel24 using UV-Vis, fluorescence, and CD spectroscopy and tried to reveal the effect of molecular structure on G-quadruplex binding [37]. To the best of our knowledge, this is a unique study revealing the effect of chain length and branching on G-quadruplex recognition.…”

Section: Introductionmentioning

confidence: 99%

Targeting human telomeric DNA with azacyanines

Doğu¹,

Çetinkol²

2019

Turk J Chem

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Small molecules targeting telomeric DNA or its interactions with telomerase have been an active area of cancer research. In the present study, we investigated the interactions of six benzimidazole compounds, called azacyanines, differing from each other in alkyl chain length and branching in the benzimidazole ring (azamethyl, azaethyl, azapropyl, azaisopropyl, azabutyl, and azaisobutyl) with human telomeric DNA (tel24) in 1:1 and 1:6 ratio (tel24:azacyanine) using UV-Vis, circular dichroism (CD), and fluorescence spectroscopy. All the compounds were binding to tel24 as indicated by the formation of the weak induced CD band between 320 nm and 360 nm. A substantial red shift and hypochromic effect were observed in the UV-Vis spectrum of azamethyl or azabutyl upon binding to tel24. No red shift or hypochromic effect was observed in the spectrum of azaisopropyl. The denaturation temperature (T m) of tel24 increased the most, from 65 • C to 78 • C, in the presence of azabutyl in 1:6 ratio. Azaisopropyl stabilized tel24 the least under the same conditions. The highest (7.84 × 10 5 ± 3.44 × 10 4 M −1) and the lowest (2.04 × 10 5 ± 5.38 × 10 4 M −1) association constants were obtained for azabutyl and azaisopropyl, respectively, by fluorescence spectroscopy. Overall, the benzimidazole scaffold, the one-pot synthesis, and the stabilization ability of azacyanines to tel24 make them plausible drug candidate molecules in targeting G-quadruplexes.

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Selective High Binding Affinity of Azacyanines to polyd(A) polyd(T)⋅polyd(T) Triplex: The Effect of Chain Length and Branching on Stabilization, Selectivity and Affinity

Cited by 2 publications

References 37 publications

Novel Fluorescent Azacyanine Compounds: Improved Synthesis and Optical Properties

Novel Fluorescent Azacyanine Compounds: Improved Synthesis and Optical Properties

Targeting human telomeric DNA with azacyanines

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