Targeting human telomeric DNA with azacyanines

Authors : Ayça Küçükakdağ DOĞU, Özgül Persil ÇETİNKOL

Pages : 1040-1051

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Publication Date : 0000-00-00

Article Type : Research Paper

Abstract :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 insert ignore into journalissuearticles values(azamethyl, azaethyl, azapropyl, azaisopropyl, azabutyl, and azaisobutyl); with human telomeric DNA insert ignore into journalissuearticles values(tel24); in 1:1 and 1:6 ratio insert ignore into journalissuearticles values(tel24:azacyanine); using UV-Vis, circular dichroism insert ignore into journalissuearticles values(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 insert ignore into journalissuearticles values(T$_{m});$ of tel24 increased the most, from 65~$^{\circ}$C to 78 $^{\circ}$C, in the presence of azabutyl in 1:6 ratio. Azaisopropyl stabilized tel24 the least under the same conditions. The highest insert ignore into journalissuearticles values(7.84 $\times $ 10$^{5} ~ \pm $ 3.44 $\times $ 10$^{4}$ M$^{-1});$ and the lowest insert ignore into journalissuearticles values(2.04 $\times $ 10$^{5\, }\pm $ 5.38 $\times $ 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.
Keywords : G quadruplex, human telomeric DNA, azacyanine, small molecule binding, intercalation