Molecular rec§ognition of telomere DNA sequence by 2, 6 anthraquinone derivatives leads to thermal stabilization and induces apoptosis in cancer cells

Dey, Arpita; Pandav, Kumud; Nath, Mala; Barthwal, Ritu; Prasad, Ramasare

doi:10.1016/j.ijbiomac.2022.08.156

Cited by 7 publications

(22 citation statements)

References 53 publications

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“…Very recently, Dey et al. demonstrated that two intervening methylene groups in the 2,6‐side‐chains of anthraquinone derivatives are more effective G‐quadruplex based drug candidates than one intervening methylene group attached side‐chain [65] . The reported binding affinity constants (∼10 6 M −1 ), as well as IC 50 values in MCF7 cell lines, corroborate the findings of the present work confirming the potency of utilizing anthraquinone derivatives in the G‐quadruplex mediated anticancer therapeutics.…”

Section: Resultsmentioning

confidence: 99%

Deciphering the Binding Insights of Novel Disubstituted Anthraquinone Derivatives with G‐Quadruplex DNA to Exhibit Selective Cancer Cell Cytotoxicity

2022

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Anthraquinone‐based compounds are well‐known as duplex DNA as well as G‐quadruplex DNA binders. Implications of various anthraquinone derivatives for specific recognition of G‐quadruplex DNA over duplex DNA is a ‘challenging’ research work that requires adequate experience with molecular design. To address this important issue, we designed and synthesized ten new 2,6‐disubstituted anthraquinone‐based derivatives with different functionalized piperazinyl side‐chains. Among these, particular compounds with certain distant groups have shown selective and significant binding affinities toward the c‐MYC and c‐KIT G‐quadruplex DNA over the duplex DNA, as noticed from various biophysical experiments. The structural difference of quadruplex and duplex DNA was utilized to probe these derivatives for the end‐stacking mode of binding with G‐quadruplex DNA. The ability of the ligands to halt DNA synthesis by stabilizing G‐quadruplex structures is one of the crucial points to further apply them for quadruplex‐mediated anti‐cancer therapeutics. Interestingly, these ligands trigger apoptosis to exhibit selective cytotoxicity toward cancer cells over normal cells. This was further evidenced by ligand‐induced cell cycle arrest as well as cellular apoptotic morphological changes. These blood‐compatible ligands provided detailed structure‐activity relationship approaches for the molecular design of anthraquinone‐based G‐quadruplex binders.

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Section: Resultsmentioning

confidence: 99%

Deciphering the Binding Insights of Novel Disubstituted Anthraquinone Derivatives with G‐Quadruplex DNA to Exhibit Selective Cancer Cell Cytotoxicity

2022

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“…The response unit was evaluated after subtracting the corresponding flow cell 2/4 (immobilized DNA) from the reference flow cell 1/3 (HEPES buffer) to obtain the response from the bound ligand. An analysis and fitting of the data of the Response Unit were performed using the Biacore T200 evaluation software to obtain the Dissociation constant (K D ) [20].…”

Section: Surface Plasmon Resonance (Spr)mentioning

confidence: 99%

“…Varying concentrations of mosR/ndhA G4 DNA were mixed with a fixed concentration of MTX (3 µM) to reach mole equivalent ratios (D/N) of MTX Drug (D) to Nucleic acid quadruplex (N) in the range of 0.31-10. Absorbance spectra of each sample were recorded using a Bio UV-visible spectrophotometer (CARY 100, Varian, Palo Alto, CA, USA) equipped with a thermostatic cell holder and quartz cuvette (path length 1 cm) in the wavelength range of 200-800 nm [20,21]. The intrinsic binding constant was calculated using the standard equations described in the Supplementary Information along with an analysis of the data.…”

Section: Absorption Spectroscopymentioning

confidence: 99%

“…Several G-quadruplex ligands (e.g., anthraquinone derivatives, flavonoids, alkaloids, telomastatins, anthracyclines, etc. ), bind through external groove binding mode [2][3][4]20,21]. Few others, such as RHPS4, daunomycin (an anthracycline) and epiberberine alkaloid bind through stacking mode at the ends of DNA or intercalate between the G-quartets via favorable π-π interactions between the aromatic surface of the G-quartets and ligands [2][3][4]17].…”

Section: Introductionmentioning

confidence: 99%

“…MTX is a frequently used anthraquinone derivative in view of its non-cardiotoxicity because it lacks the amino sugar fragment and has a hydroxyquinone functional group with a polyamide side chain. 4,20,21]. Few others, such as RHPS4, daunomycin (an anthracycline) and epiberberine alkaloid bind through stacking mode at the ends of DNA or intercalate between the G-quartets via favorable π-π interactions between the aromatic surface of the G-quartets and ligands [2][3][4]17].…”

Section: Introductionmentioning

confidence: 99%

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MOSR and NDHA Genes Comprising G-Quadruplex as Promising Therapeutic Targets against Mycobacterium tuberculosis: Molecular Recognition by Mitoxantrone Suppresses Replication and Gene Regulation

Dey

Anand

Singh

et al. 2023

Genes

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Occurrence of non-canonical G-quadruplex (G4) DNA structures in the genome have been recognized as key factors in gene regulation and several other cellular processes. The mosR and ndhA genes involved in pathways of oxidation sensing regulation and ATP generation, respectively, make Mycobacterium tuberculosis (Mtb) bacteria responsible for oxidative stress inside host macrophage cells. Circular Dichroism spectra demonstrate stable hybrid G4 DNA conformations of mosR/ndhA DNA sequences. Real-time binding of mitoxantrone to G4 DNA with an affinity constant ~105–107 M−1, leads to hypochromism with a red shift of ~18 nm, followed by hyperchromism in the absorption spectra. The corresponding fluorescence is quenched with a red shift ~15 nm followed by an increase in intensity. A change in conformation of the G4 DNA accompanies the formation of multiple stoichiometric complexes with a dual binding mode. The external binding of mitoxantrone with a partial stacking with G-quartets and/or groove binding induces significant thermal stabilization, ~20–29 °C in ndhA/mosR G4 DNA. The interaction leads to a two/four-fold downregulation of transcriptomes of mosR/ndhA genes apart from the suppression of DNA replication by Taq polymerase enzyme, establishing the role of mitoxantrone in targeting G4 DNA, as an alternate strategy for effective anti-tuberculosis action in view of deadly multi-drug resistant tuberculosis disease causing bacterial strains t that arise from existing therapeutic treatments.

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Investigating the preferential interaction between imatinib mesylate and VEGF G-quadruplex DNA as therapeutic strategies for cancer treatment: Biophysical and molecular modelling approaches

Ghosal,

Bag,

Chinnadurai

et al. 2024

Computers in Biology and Medicine

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Molecular rec§ognition of telomere DNA sequence by 2, 6 anthraquinone derivatives leads to thermal stabilization and induces apoptosis in cancer cells

Cited by 7 publications

References 53 publications

Deciphering the Binding Insights of Novel Disubstituted Anthraquinone Derivatives with G‐Quadruplex DNA to Exhibit Selective Cancer Cell Cytotoxicity

Deciphering the Binding Insights of Novel Disubstituted Anthraquinone Derivatives with G‐Quadruplex DNA to Exhibit Selective Cancer Cell Cytotoxicity

MOSR and NDHA Genes Comprising G-Quadruplex as Promising Therapeutic Targets against Mycobacterium tuberculosis: Molecular Recognition by Mitoxantrone Suppresses Replication and Gene Regulation

Investigating the preferential interaction between imatinib mesylate and VEGF G-quadruplex DNA as therapeutic strategies for cancer treatment: Biophysical and molecular modelling approaches

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