Tröger's base scaffold in racemic and chiral fashion as a spacer for bisdistamycin formation. Synthesis and DNA binding study

Valík, Martin; Malina, Jaroslav; Palivec, Lukáš; Foltýnová, Jarmila; Tkadlecová, Marcela; Urbanová, Marie; Brabec, Viktor; Král, Vladimı́r

doi:10.1016/j.tet.2006.06.056

Cited by 30 publications

(13 citation statements)

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“…Didier and Sergeyev synthesized a few symmetrical amino and amino ethyl Tröger's base derivatives via Pd catalyzed C-C and C-N bond formation [18]. Tröger's base derivatives are also used as catalysts for organic synthesis-construction of new supramolecular hosts [19,20], complexation [21], diastereoselective self-assembly of double standard helicates [21,23], molecular tweezers [24,25], scaffolds [26,27] and HPLC chromophoric solid phase supporters [28][29][30]. The synthesis of pure optically active Ru(II) complexes with a chiral Tröger's base ligands and their interaction towards DNA was investigated by Classens et al, [31].…”

Section: Introductionmentioning

confidence: 99%

NMR Spectral Correlations in Some Tröger’s Bases

Thirunarayanan

Suresh

2013

ILCPA

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Some Tröger's bases have been synthesised from substituted anilines and paraformaldehyde in presence of Lewis acid catalyst such as anhydrous AlCl 3 , through electrophilic substitution reaction. The purities of these Tröger's bases have been checked by their physical constants and spectroscopic data published earlier in the literature. The NMR chemical shift (δ, ppm) of methylene protons and carbon were assigned. The assigned methylene protons and carbon chemical shifts (δ, ppm) of synthesised Tröger's bases have been correlated with Hammett substituent constants, F and R parameters using single and multi-regression analyses. From the results of statistical analyses, the effects of substituent on methylene protons and carbon were discussed.

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Section: Introductionmentioning

confidence: 99%

NMR Spectral Correlations in Some Tröger’s Bases

Thirunarayanan

Suresh

2013

ILCPA

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“…There is limited research investigating the chirality effect of minor groove binders on DNA interaction. The dimerization of two N-methylpyrrole oligopeptides through the chiral linker methanodiazocin scaffold has shown that the (4R,9R)-form is better suited for interaction with calf thymus DNA than the (4S,9S)-form [8]. In addition, Herman et al (1998) has shown that the enantiomer derived from two distamycin A-derived polyamides linked by either (R)-2,4-diaminobutyric acid showed enhanced binding affinity towards DNA when compared to the (S)-2,4-diaminobutyric acid-enantiomer [9].…”

Section: Introductionmentioning

confidence: 99%

Impact of pyrrolidine-bispyrrole DNA minor groove binding agents and chirality on global proteomic profile in Escherichia Coli

et al. 2013

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BackgroundThere is great interest in the design of small molecules that selectively target minor grooves of duplex DNA for controlling specific gene expression implicated in a disease. The design of chiral small molecules for rational drug design has attracted increasing attention due to the chirality of DNA. Yet, there is limited research on the chirality effect of minor groove binders on DNA interaction, especially at the protein expression level. This paper is an attempt to illustrate that DNA binding affinity might not provide a full picture on the biological activities. Drug interacting at the genomic level can be translated to the proteomic level. Here we have illustrated that although the chiral bispyrrole-pyrrolidine-oligoamides, PySSPy and PyRSPy, showed low binding affinity to DNA, their influence at the proteomic level is significant. More importantly, the chirality also plays a role. Two-dimensional proteomic profile to identify the differentially expressed protein in Escherichia coli DH5α (E coli DH5α) were investigated.ResultsE coli DH5α incubated with the chiral PySSPy and PyRSPy, diastereomeric at the pyrrolidine ring, showed differential expression of eighteen proteins as observed through two dimensional proteomic profiling. These eighteen proteins identified by MALDI_TOF/TOF MS include antioxidant defense, DNA protection, protein synthesis, chaperone, and stress response proteins. No statistically significant toxicity was observed at the tested drug concentrations as measured via MTT assay.ConclusionThe current results showed that the chiral PySSPy and PyRSPy impact on the proteomic profiling of E coli DH5α, implicating the importance of drug chirality on biological activities at the molecular level.

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“…13,14 According to Valik et al, 10 these chiral properties make these compounds of great promise as DNA probes, since they discern between right-handed and left-handed DNA isoforms. Even so, there are very few studies regarding Tröger-DNA interactions so far [13][14][15][16][17][18] and, despite inconclusive assumptions based on spectroscopic and biochemical data, the binding mechanism of these molecules to DNA remains unknown. It has been suggested that the levorotatory isomer of a symmetric proflavine Tröger base (Figure1B) is more likely to interact through minor groove binding, although proflavine is a known intercalating agent.…”

Section: Introductionmentioning

confidence: 99%