Binding of anticancer drug daunomycin to parallel G-quadruplex DNA [d-(TTGGGGT)]4 leads to thermal stabilization: A multispectroscopic investigation

Tariq, Zia; Barthwal, Ritu

doi:10.1016/j.ijbiomac.2018.09.154

Cited by 22 publications

(46 citation statements)

References 67 publications

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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%

“…Several studies investigating the effect of the benzimidazole scaffold on telomeric DNA and oncogene promoters such as KRAS and VEGFR that are known to fold into quadruplex structures were recently reported [24][25][26][27][28][29][30]. In addition, several reports investigating the effect of such small molecules on different cancer lines and promoting G-quadruplexes as plausible targets in cancer therapy were also published [31][32][33][34][35][36]. 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.…”

Section: Introductionmentioning

confidence: 99%

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

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Targeting human telomeric DNA with azacyanines

Doğu¹,

Çetinkol²

2019

Turk J Chem

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“…In the current study, we investigated unusually large H/D isotope effects on the interaction of our redox marker molecules and DNA layers observed in voltammetry. We have extended our isotope study towards small organic drug molecules such as daunomycin, which are known to interact mainly with dsDNA, preferably G‐quadruplex structures by intercalation, end stacking, groove binding and even external binding . Daunomycin is one of the most commonly used anthracycline anticancer drugs, mainly for breast and ovarian cancer, thyroid carcinomas and acute lymphocytic leukemia.…”

Section: Figurementioning

confidence: 99%

“…We have extended our isotope study towards small organic drug molecules such as daunomycin, which are known to interact mainly with dsDNA, preferably G-quadruplex structures by intercalation, end stacking, groove binding and even external binding. [45] Daunomycin is one of the most commonly used anthracycline anticancer drugs, mainly for breast and ovarian cancer, thyroid carcinomas and acute lymphocytic leukemia. Many electrochemical investigations have been made with daunomycin by aptamer immobilization [46] and in solution with chronopotentiometric stripping analysis, [47] due to its two electroactive sites: a reducible quinone center and oxidizable hydroquinone group.…”

Section: Voltammetric H/d Isotope Effects On Redox-active Small Molecmentioning

confidence: 99%

Voltammetric H/D Isotope Effects on Redox‐Active Small Molecules Conjugated with DNA Self‐Assembled Monolayers

Galagedera

Flechsig

2019

ChemElectroChem

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This paper describes the largest H/D kinetic isotope effect (KIE) at room temperature (25 °C) reported to date (kH/kD=2400). In voltammetric measurements with DNA monolayers on gold electrodes, a maximum shift of −400 mV was recorded for the reduction peak potential of 50 μM hexammine cobalt(III) (CoHex) in 10 mM Tris buffer upon replacing water with deuterium oxide in the electrolyte. In subsequent comparative investigations, a much smaller shift (ca. −80 mV) was recorded with daunomycin, whereas no potential shift was recorded with hexammine ruthenium(III) (RuHex). The interactions of RuHex, CoHex, and daunomycin with a mixed self‐assembled monolayer of single‐stranded DNA and 6‐mercapto‐1‐hexanol (ssDNA/MCH SAM) immobilized on gold electrodes were studied by using cyclic and differential‐pulse voltammetry (CV and DPV, respectively). The hydrogen‐bond network within the ssDNA layer seems to amplify the voltammetric H/D isotope effect with CoHex. Voltammetric studies of H/D isotope effects can provide a platform to investigate amplified isotope effects probably not only on DNA layers, but also on proteins and small organic molecules and may be useful for studies of cell proliferation as well as drug testing.

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“…Besides, long telomeric sequences existing in several folded forms with different topologies form inter molecular aggregates making interpretation of results on ligand‐intra molecular G‐quadruplex complex very difficult. Inter molecular quadruplexes have therefore been used in past as motifs to get high resolution data on drug‐DNA interactions for various ligands using X‐ray/NMR techniques, which is necessary to understand their molecular basis of action. X‐ray crystallographic structure of daunomycin co‐crystallized with inter molecular hexameric G‐quadruplex DNA [d‐(TGGGGT)] 4 , containing telomeric DNA sequence from Tetrahymena thermophila , showed two layers of daunomycin, each containing three molecules, sandwiched between two G4 DNA molecules stacked end to end .…”

Section: Introductionmentioning

confidence: 99%

Binding of anticancer drug adriamycin to parallel G‐quadruplex DNA [d‐(TTAGGGT)]₄ comprising human telomeric DNA leads to thermal stabilization: A multiple spectroscopy study

Raje

Pandav

Barthwal

2019

J of Molecular Recognition

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Adriamycin is known to exert its anti cancer action by inhibiting DNA duplication, RNA transcription and topoisomerase-II enzyme action. Recent findings of its binding to G-quadruplex DNA resulting in telomere dysfunction indicated multiple strategies of its action. The interaction of anticancer drug adriamycin with parallel stranded inter molecular G-quadruplex DNA [d-(TTAGGGT)] 4 comprising human telomeric DNA sequence TTAGGG was investigated by absorption, fluorescence, circular dichroism and nuclear magnetic resonance spectroscopy to understand mode of their interaction. The adriamycin binds as monomer to G-quadruplex DNA with affinity (K b1 = 9.8x10 5 M −1 and K b2 = 6.7x10 5 M −1 ) higher than that reported for daunomycin, at two independent sites, mainly in terminal stacking and groove binding modes.The bound complex formed as a result of specific interactions induces thermal stabilization of DNA by 12.5-28.1 C, which is likely to hinder telomere association with telomerase enzyme and contribute significantly to adriamycin-induced apoptosis in cancer cell lines. The findings have therapeutic potential towards drug designing by way of altering substituent groups on anthracyclines to enhance efficacy using additional mechanism of targeting pathway of telomere maintenance by disrupting telomerase association with telomeres.

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Binding of anticancer drug daunomycin to parallel G-quadruplex DNA [d-(TTGGGGT)]4 leads to thermal stabilization: A multispectroscopic investigation

Cited by 22 publications

References 67 publications

Targeting human telomeric DNA with azacyanines

Targeting human telomeric DNA with azacyanines

Voltammetric H/D Isotope Effects on Redox‐Active Small Molecules Conjugated with DNA Self‐Assembled Monolayers

Binding of anticancer drug adriamycin to parallel G‐quadruplex DNA [d‐(TTAGGGT)]₄ comprising human telomeric DNA leads to thermal stabilization: A multiple spectroscopy study

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Binding of anticancer drug daunomycin to parallel G-quadruplex DNA [d-(TTGGGGT)]4 leads to thermal stabilization: A multispectroscopic investigation

Cited by 22 publications

References 67 publications

Targeting human telomeric DNA with azacyanines

Targeting human telomeric DNA with azacyanines

Voltammetric H/D Isotope Effects on Redox‐Active Small Molecules Conjugated with DNA Self‐Assembled Monolayers

Binding of anticancer drug adriamycin to parallel G‐quadruplex DNA [d‐(TTAGGGT)]4 comprising human telomeric DNA leads to thermal stabilization: A multiple spectroscopy study

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Binding of anticancer drug adriamycin to parallel G‐quadruplex DNA [d‐(TTAGGGT)]₄ comprising human telomeric DNA leads to thermal stabilization: A multiple spectroscopy study