Bisindolylmaleimides Linked to DNA Minor Groove Binding Lexitropsins:  Synthesis, Inhibitory Activity against Topoisomerase I, and Biological Evaluation

Abstract DNA intercalating and minor groove binding compounds are new weapons in the battle against malignant diseases. These antineoplastic agents target the DNA molecule and interfere with the cell cycle leading to rapidly proliferating cell death. They are mainly derivates of a naturally occurring organic compound derived from a microorganism or plant. Intercalators usually act as topoisomerase I and/or II poisons, while the mechanisms of DNA minor groove binders are a combination of several steps including topoisomerase poisoning. This paper gives an overview of some of the developed DNA intercalating and minor groove binding compounds, as well as an explanation of their chemical structures, origins, and application in chemotherapy.

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Synthesis, determination of sequence selective DNA minor groove binding and biological evaluation of hybrid bithiazole-linked netropsin derivatives

European Journal of Medicinal Chemistry ◽

10.1016/0223-5234(92)90146-r ◽

1992 ◽

Vol 27 (4) ◽

pp. 331-344 ◽

Cited By ~ 1

Author(s):

D Mrani ◽

G Gosselin ◽

C Bailly ◽

R Houssin ◽

KE Rao ◽

...

Keyword(s):

Minor Groove ◽

Biological Evaluation ◽

Minor Groove Binding ◽

Groove Binding ◽

Dna Minor Groove

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Design, synthesis, and evaluation of DNA minor groove binding agents: the duocarmycins

Pure and Applied Chemistry ◽

10.1351/pac199466040837 ◽

1994 ◽

Vol 66 (4) ◽

pp. 837-844 ◽

Cited By ~ 17

Author(s):

D. L. Boger

Keyword(s):

Minor Groove ◽

Minor Groove Binding ◽

Groove Binding ◽

Design Synthesis ◽

Dna Minor Groove ◽

Binding Agents

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Influence of GC and AT Specific DNA Minor Groove Binding Drugs on Intermolecular Triplex Formation in the Human c-Ki-ras Promoter†

Biochemistry ◽

10.1021/bi951562b ◽

1996 ◽

Vol 35 (4) ◽

pp. 1106-1114 ◽

Cited By ~ 12

Author(s):

Nadarajah Vigneswaran ◽

Charles A. Mayfield ◽

Brad Rodu ◽

Roger James ◽

H.-G. Kim ◽

...

Keyword(s):

Minor Groove ◽

Minor Groove Binding ◽

Groove Binding ◽

Dna Minor Groove ◽

Triplex Formation

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DNA Minor Groove Binding with Bisbenzamidine-Ru(II) Complexes

10.26434/chemrxiv.8118995.v1 ◽

2019 ◽

Author(s):

Mateo I. Sánchez ◽

Gustavo Rama ◽

Renata Calo ◽

Kübra Ucar ◽

Per Lincoln ◽

...

Keyword(s):

Dna Cleavage ◽

Coordination Compounds ◽

Photophysical Properties ◽

Organic Ligand ◽

Minor Groove ◽

The Other ◽

Minor Groove Binding ◽

Binding Agent ◽

Groove Binding ◽

Dna Minor Groove

We report the first Ru(II) coordination compounds that interact with DNA through a canonical minor groove insertion mode and with selectivity for A/T rich sites. This was made possible by integrating a bis‑benzamidine minor groove DNA-binding agent with a ruthenium(II) complex. Importantly, one of the enantiomers (Δ‑[Ru(bpy)2b4bpy]2+, Δ‑4Ru) shows a considerably higher DNA affinity than the parent organic ligand and than the other enantiomer, particularly for the AATT sequence, while the other enantiomer preferentially targets long AAATTT sites with overall lower affinity. Finally, we demonstrate that the photophysical properties of these new binders can be exploited for DNA cleavage using visible light.

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