Novel DNA Bis-Intercalator XR5944 as a Potent Anticancer Drug—Design and Mechanism of Action

This review is dedicated to Professor William A. Denny’s discovery of XR5944 (also known as MLN944). XR5944 is a DNA-targeted agent with exceptionally potent antitumor activity and a novel DNA binding mode, bis-intercalation and major groove binding, as well as a novel mechanism of action, transcription inhibition. This novel anticancer compound represents a remarkable accomplishment resulting from two decades of drug discovery by Professor Denny and coworkers. Here, we review our work on the structural study of the DNA binding mode of XR5944 and mechanistic study of XR5944 action.

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Governing the DNA-binding mode of styryl dyes by the length of their alkyl substituents – from intercalation to major groove binding

Organic & Biomolecular Chemistry ◽

10.1039/c7ob02736b ◽

2018 ◽

Vol 16 (4) ◽

pp. 545-554 ◽

Cited By ~ 17

Author(s):

Daria V. Berdnikova ◽

Nikolai I. Sosnin ◽

Olga A. Fedorova ◽

Heiko Ihmels

Keyword(s):

Dna Binding ◽

Binding Mode ◽

Major Groove ◽

Groove Binding ◽

Styryl Dyes

The length of alkyl substituents governs the DNA binding mode of mono- and bis-chromophoric styryl dyes.

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Dimeric and trimeric derivatives of the azinomycin B chromophore show enhanced DNA binding

Organic & Biomolecular Chemistry ◽

10.1039/c7ob00944e ◽

2017 ◽

Vol 15 (21) ◽

pp. 4522-4526 ◽

Cited By ~ 4

Author(s):

Milena Balazy ◽

Alejandra Fausto ◽

Christina Voskanian ◽

Bianca Chavez ◽

Harmanpreet Panesar ◽

...

Keyword(s):

Dna Binding ◽

Major Groove ◽

Groove Binding ◽

Azinomycin B ◽

Derivatives Of

Compound1d(Kapp= 2.4 × 107M−1), a derivative of the azinomycin B chromophore, strongly associates with DNA by intercalation and major groove binding.

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From Intercalation to Groove Binding: Switching the DNA-Binding Mode of Isostructural Transition-Metal Complexes

Chemistry - A European Journal ◽

10.1002/chem.201304053 ◽

2014 ◽

Vol 20 (11) ◽

pp. 3089-3096 ◽

Cited By ~ 22

Author(s):

Haslina Ahmad ◽

Ashley Wragg ◽

Will Cullen ◽

Claire Wombwell ◽

Anthony J. H. M. Meijer ◽

...

Keyword(s):

Dna Binding ◽

Transition Metal ◽

Metal Complexes ◽

Transition Metal Complexes ◽

Binding Mode ◽

Groove Binding

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Structural Modification Changes the DNA Binding Mode of Cation-Substituted Anthraquinone Photonucleases: Association by Intercalation or Minor Groove Binding Determines the DNA Cleavage Efficiency†

Biochemistry ◽

10.1021/bi9702750 ◽

1997 ◽

Vol 36 (34) ◽

pp. 10463-10473 ◽

Cited By ~ 16

Author(s):

David T. Breslin ◽

Changjun Yu ◽

Danith Ly ◽

Gary B. Schuster

Keyword(s):

Dna Binding ◽

Dna Cleavage ◽

Structural Modification ◽

Binding Mode ◽

Minor Groove ◽

Minor Groove Binding ◽

Groove Binding ◽

Cleavage Efficiency

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Mitomycin C linked to DNA minor groove binding agents: synthesis, reductive activation, DNA binding and cross-linking properties and in vitro antitumor activity

Bioorganic & Medicinal Chemistry ◽

10.1016/s0968-0896(99)00223-0 ◽

1999 ◽

Vol 7 (12) ◽

pp. 2713-2726 ◽

Cited By ~ 16

Author(s):

Manuel M Paz ◽

Arunangshu Das ◽

Maria Tomasz

Keyword(s):

Dna Binding ◽

Antitumor Activity ◽

Mitomycin C ◽

Cross Linking ◽

Minor Groove Binding ◽

Reductive Activation ◽

Groove Binding ◽

Dna Minor Groove ◽

Binding Agents

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Synthesis, Characterization, DNA-Binding Study of C15H12O4N2 and its Lanthanide Complexes

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.749.516 ◽

2013 ◽

Vol 749 ◽

pp. 516-520

Author(s):

Chao Chao Song ◽

Xiang Rong Liu ◽

Shun Sheng Zhao ◽

Jun Wang ◽

Jing Wen Ren ◽

...

Keyword(s):

Dna Binding ◽

Ir Spectroscopy ◽

Elemental Analysis ◽

Lanthanide Complexes ◽

Binding Mode ◽

Binding Study ◽

Groove Binding ◽

Groove Binding Mode

A new series complexes of Ln nitrate with H2L, where Ln stands for La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Yb, and H2L is 2-carboxybenzaldehyde- (4-hydroxy) benzoylhydrazone, were synthesized. Elemental analysis and IR spectroscopy were used to characterize and found that the complexes were Ln (HL)2(NO3)·4EtOH·4H2O type. The binding mode of complexes with CTDNA was investigated by UV-Vis titration and emission titration, suggesting that the complexes bind with CTDNA in a non-covalent groove binding mode.

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