Targeting human telomeric DNA with azacyanines

Kucukakdag Dogu, Ayca
Persil Çetinkol, Özgül
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 degrees C to 78 degrees C, in the presence of azabutyl in 1:6 ratio. Azaisopropyl stabilized tel24 the least under the same conditions. The highest (7.84 x 10(5) +/- 3.44 x 10(4) M-1) and the lowest (2.04 x 10(5) +/- 5.38 x 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.


Targeting human telomeric DNA with azacyanines
Küçükakdağ Doğu, Ayça; Persil Çetinkol, Özgül; Department of Chemistry (2019)
Small molecules targeting telomeric DNA or its interactions with telomerase have been an active area of cancer research. Within this thesis, a series of five new benzimidazole compounds differing from each other in alkyl chain length and branching in the benzimidazole ring (ethyl, propyl, isopropyl, butyl, and isobutyl) were synthesized and characterized using Nuclear Magnetic Resonance (NMR) spectroscopy, High Resolution Mass spectroscopy and C/H/N elemental analysis. Their interactions with human telomeri...
Identification of gene mutations involved in drug resistance in liver cancer using RNA-SEQ data analysis
Shojaei, Mona; Atalay, Rengül; Acar, Aybar Can; Department of Bioinformatics (2016)
A significant concern in cancer research is the detection of cancer associated somatic mutations. Liver cancer is the 5th most common and 2nd deadliest cancer in the world. Several somatic mutations were previously reported in liver cancer but their relations to chemotherapeutic response was not studied in detail. In this study, the relationship between mutation status and drug treatment response of well-differentiated Huh7 and poorly-differentiated Mahlavu liver cancer cells were analyzed. The RNA-Seq data...
Selective High Binding Affinity of Azacyanines to polyd(A) center dot polyd(T) center dot polyd(T) Triplex: The Effect of Chain Length and Branching on Stabilization, Selectivity and Affinity
Tutuncu, Serra; Guloglu, Sercan; Kucukakdag, Ayca; Persil Çetinkol, Özgül (2018-12-06)
Triplex nucleic acid structures receive considerable attention due to their possible role in anti-gene therapy, several diseases as Friedreich's ataxia and Deoxyribonucleic acid (DNA) based nano-structures. The modulation of triplex formation and its stabilization using small molecules is one way to enhance their utility in such applications. Here, we synthesized five new Azacyanines (Azaethyl (2 b), Azapropyl (2 c), Azaisopropyl (2 d), Azabutyl (2 e), Azaisobutyl (2 f)) and assessed their affinity and sele...
Targeted delivery of CPG-oligodeoxynucleotide to breast cancer cells by poly-amidoamine dendrimer-modified magnetic nanoparticles
Taghavi Pourianazar, Negar; Gündüz, Ufuk; Gündüz, Güngör; Department of Biotechnology (2016)
One major application of nanotechnology in cancer treatment involves designing nanoparticles to deliver drugs, oligonucleotides, and genes to cancer cells. Nanoparticles should be engineered so that they could target and destroy tumor cells with minimal damage to healthy tissues. This research aims to develop an appropriate and efficient nanocarrier, having the ability of interacting with and delivering CpG-oligodeoxynucleotides (CpG-ODNs) to tumor cells. CpG-ODNs activate Toll-like receptor 9 (TLR9), which...
Targeted Drug Delivery via Chitosan-Coated Magnetic Nanoparticles
Unsoy, Gözde; Gündüz, Ufuk (Elsevier, 2017-01-01)
The devastating effects of chemotherapeutic agents have been observed on healthy cells as well as tumor cells because they are nonspecifically distributed all over the body. This treatment results in hazardous side effects and excessive toxicity. Targeted drug delivery has emerged to overcome the lack of specificity of conventional chemotherapy. Nanoparticles used for drug targeting are promising to circumvent these challenges, by enabling the localization of high drug amounts at the site of disease. When d...
Citation Formats
A. Kucukakdag Dogu and Ö. Persil Çetinkol, “Targeting human telomeric DNA with azacyanines,” TURKISH JOURNAL OF CHEMISTRY, pp. 1040–1051, 2019, Accessed: 00, 2020. [Online]. Available: