Targeting human telomeric DNA with azacyanines

Küçükakdağ Doğu, Ayça
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 telomeric DNA (tel24) along with the previously investigated methyl derivative were investigated using UV-VIS, Circular Dichroism, and Fluorescence spectroscopy. All the compounds were found to be binding to tel24 and inducing a weak CD band between 320 nm and 360 nm in 1:1 complexes. Substantial red-shift and hypochromic effect were observed only in the UV-VIS spectrum of Azamethyl and Azabutyl upon binding to tel24. No red shift or hypochromic effect was observed in the UV-VIS spectrum of Azaisopropyl in the presence of tel24. Among the compounds investigated, the butyl derivative was found to be binding to tel24 tighter than the previously investigated methyl derivative. Association constants were found to be 6.61x105 ± (3.74x104 ), 7.84x105 ± (3.44x104 ), and 4.55x105 ± (1.23x104 ) M-1 for Azamethyl, Azabutyl, and Azaisobutyl respectively. Azaisopropyl showed the lowest binding affinity towards tel24. As a result, this study revealed that tel24 was a specific target for Azamethyl, Azabutyl, vi and Azaisobutyl and azacyanines might be plausible drug candidate molecules in targeting G-quadruplexes.


Targeting human telomeric DNA with azacyanines
Kucukakdag Dogu, Ayca; Persil Çetinkol, Özgül (2019-01-01)
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 fluore...
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...
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...
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...
Highly-sensitive and fast detection of human telomeric G-Quadruplex DNA based on a hemin-conjugated fluorescent metal-organic framework platform
Javan Kouzegaran, Vahid; Farhadi, Khalil; Forough, Mehrdad; Bahram, Morteza; Persil Çetinkol, Özgül (Elsevier BV, 2021-04-15)
© 2021 Elsevier B.V.The formation of G-quadruplex (G4) structures in Human telomeric DNA (H-Telo) has been demonstrated to inhibit the activity of telomerase enzyme that is associated with the proliferation of many cancer cells. Accordingly, G-quadruplex structures have become one of the well-established targets in anticancer therapeutic strategies. And, the development of simple and selective detection platforms for G4 structures has become a significant focus of research in recent years. In this study, a ...
Citation Formats
A. Küçükakdağ Doğu, “Targeting human telomeric DNA with azacyanines,” Thesis (M.S.) -- Graduate School of Natural and Applied Sciences. Chemistry., Middle East Technical University, 2019.