Selective interaction between tylophorine B and bulged DNA

Xi, Zhen; Zhang, Ruoyu; Yu, Zhihong; Ouyang, Dongyan; Huang, Runqiu

doi:10.1016/j.bmcl.2005.02.022

Cited by 55 publications

(18 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, the G-repeated sequence used here has an A inserted between 4 continuous G and, in compensation, the other 3 sequences all have an extra nucleotide end added at both 5′ and 3′ ends, respectively. All of the 4 hairpins were originally chemically synthesized as single strands and afterwards annealed to form the hairpin structures [13,19]. Unlike CT-DNA or any other standard double-helical DNA, the CD spectra of such short sequences (online suppl.…”

Section: Resultsmentioning

confidence: 99%

“…They were first synthesized linearly and then annealed to form the hairpin and duplex structures before use. Annealing of strands to form duplexes was accomplished by heating of the solution at 95°C for 5 min and then slow cooling to room temperature, followed by refrigeration for 30 min to ensure the formation of hairpins or duplexes [13]. The concentration of CT-DNA was calculated by the amount of base pairs [ M (bp)] [10], and that of hairpin polynucleotides was calculated by the amount of base pairs [ M (bp)] of their duplex parts.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Interaction Studies of an Anticancer Alkaloid, (+)-(13aS)-Deoxytylophorinine, with Calf Thymus DNA and Four Repeated Double-Helical DNAs

Liu¹,

Li³

et al. 2011

Chemotherapy

View full text Add to dashboard Cite

Background: Phenanthroindolizidine alkaloids are a family of plant-derived compounds with significant antineoplastic activity. The specific biomolecular targets of these alkaloids have not yet been clearly identified. (+)-(13aS)-deoxytylophorinine is a new phenanthroindolizidine alkaloid originally extracted from the roots of Tylophora atrofolliculata and Tylophora ovata in our institute. (+)-(13aS)-deoxytylophorinine exerts both in vitro and in vivoanticancer activities. Methods: The in vivo anticancer effects and toxicity of this compound were investigated in mice, and interactions between this compound and double-helical DNA sequences were studied in detail with circular dichroic spectroscopy and fluorescence spectroscopy. Viscosity measurements were applied to check the interactive mode between this compound and DNA. Results: Potent anticancer effects were observed in vivo. Also, concentration-dependent interactions were observed and this compound seemed to interact in a sequence-specific manner with AT-repeated sequences of double-helical DNA. Such interactions were proved to be intercalating by viscosity measurements. Conclusions: Anticancer alkaloid (+)-(13aS)-deoxytylophorinine can have sequence-specific interactions with DNA in an intercalating manner.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Interaction Studies of an Anticancer Alkaloid, (+)-(13aS)-Deoxytylophorinine, with Calf Thymus DNA and Four Repeated Double-Helical DNAs

Liu¹,

Li³

et al. 2011

Chemotherapy

View full text Add to dashboard Cite

show abstract

“…5 Compound 1a also interacts with the bulged regions of DNA and RNA. 6,7 Due to low natural abundance of this compound type, various syntheses of 1a and other phenanthroindolizidine alkaloids, in both racemic and optically active forms, have been reported in an effort to further investigate the biochemical and pharmaceutical effects. [8][9][10][11][12][13][14] The most commonly reported synthetic methodology toward the highly condensed natural alkaloids (±)-1a and its geometric isomer (±)-deoxypergularinine (1b) involves formation of the biaryl bond of the phenanthrene ring system in the final step, after coupling of the aromatic residues with the appropriate heterocycle.…”

Section: Introductionmentioning

confidence: 99%

Total synthesis of phenanthroindolizidine alkaloids (±)-antofine, (±)-deoxypergularinine, and their dehydro congeners and evaluation of their cytotoxic activity

Damu

Chiang

et al. 2008

Bioorganic & Medicinal Chemistry

View full text Add to dashboard Cite

Due to their limited natural abundance and significant biochemical effects, we synthesized the alkaloids (±)-antofine (1a), (±)-deoxypergularinine (1b), and their dehydro congeners (2 and 3) starting from the corresponding phenanthrene-9-carboxaldehydes. We also evaluated their in vitro cytotoxic activity. Compounds 1a and 1b showed significant potency against various human tumor cell lines, including a drug-resistant variant, with EC 50 values ranging from 0.16-16 ng/mL. Structure-activity correlations of these alkaloids and some of their synthetic intermediates were also ascertained. The non-planar structure between the two major moieties, phenanthrene and indolizidine, plays a crucial role in the cytotoxic activity of phenanthroindolizidines. Increasing the planarity and rigidity of the indolizidine moiety significantly reduced potency. A methoxy group at the 2-position (1a) was more favorable for cytotoxic activity than a hydrogen atom (1b).

show abstract

“…The changed T m values of the duplexes [T m of the duplex modified by the helicate À T m of the control (unmodified duplex) (DT m )] are generally affected by the oligonucleotides' dissociation constants and the stability of their own secondary structures. The stronger the interaction between DNA and [Fe 2 L 3 ] 4+ , the more the T m value increases [26,27].…”

Section: Uv Melting Studiesmentioning

confidence: 99%

Recognition of DNA bulges by dinuclear iron(II) metallosupramolecular helicates

2014

View full text Add to dashboard Cite

Bulged DNA structures are of general biological significance because of their important roles in a number of biochemical processes. Compounds capable of targeting bulged DNA sequences can be used as probes for studying their role in nucleic acid function, or could even have significant therapeutic potential. The interaction of [Fe 2 L 3 ] 4+ metallosupramolecular helicates (L = C 25 H 20 N 4 ) with DNA duplexes containing bulges has been studied by measurement of the DNA melting temperature and gel electrophoresis. This study was aimed at exploring binding affinities of the helicates for DNA bulges of various sizes and nucleotide sequences. The studies reported herein reveal that both enantiomers of [Fe 2 L 3 ] 4+ bind to DNA bulges containing at least two unpaired nucleotides. In addition, these helicates show considerably enhanced affinity for duplexes containing unpaired pyrimidines in the bulge and/or pyrimidines flanking the bulge on both sides. We suggest that the bulge creates the structural motif, such as the triangular prismatic pocket formed by the unpaired bulge bases, to accommodate the [Fe 2 L 3 ] 4+ helicate molecule, and is probably responsible for the affinity for duplexes with a varying number of bulge bases. Our results reveal that DNA bulges represent another example of unusual DNA structures recognized by dinuclear iron(II) ([Fe 2 L 3 ] 4+ ) supramolecular helicates.

show abstract

Selective interaction between tylophorine B and bulged DNA

Cited by 55 publications

References 21 publications

Interaction Studies of an Anticancer Alkaloid, (+)-(13aS)-Deoxytylophorinine, with Calf Thymus DNA and Four Repeated Double-Helical DNAs

Interaction Studies of an Anticancer Alkaloid, (+)-(13aS)-Deoxytylophorinine, with Calf Thymus DNA and Four Repeated Double-Helical DNAs

Total synthesis of phenanthroindolizidine alkaloids (±)-antofine, (±)-deoxypergularinine, and their dehydro congeners and evaluation of their cytotoxic activity

Recognition of DNA bulges by dinuclear iron(II) metallosupramolecular helicates

Contact Info

Product

Resources

About