Synthesis and Biophysical Evaluation of 7,8-(Alkylenedioxy)-Flavones
Poster Number
9B
Research or Creativity Area
Natural Sciences
Abstract
Triplex DNA is formed when a third strand, the triplex-forming oligonucleotide (TFO), sequence specifically binds to a duplex. TFOs are considered for anti-gene therapy in which a certain sequence of duplex DNA can be targeted, and triplex formation will regulate the downstream transcription and translation of a mutated protein. However, triplex formation is limited in both thermodynamic and kinetic aspects. Recently, it was found that a flavonoid, quercetin, and its derivatives were able to stabilize triplex DNA without having an effect on duplex DNA. Flavonoids are naturally derived metabolites from plants that have been found to have a variety of roles, including anti-inflammatory, anti-oxidative, anti-bacterial, and anti-carcinogenic effects. From this discovery, a variety of natural flavonoids have been tested against triplex DNA in our lab, and two compounds that stood out were α- and 𝛽- naphthoflavone, which, despite their similarity in structure, only α-naphthoflavone had a significant triplex stabilization effect. Based on this, we designed a synthesis scheme using 7,8-dihydroxyflavone as the starting material for the construction of an aliphatic ring to replace the fused benzene ring in α-naphthoflavone and yield a series of 7,8-(alkylenedioxy)- flavone derivatives. A total of nine derivatives have been synthesized with varying yields and evaluated for purity using NMR. These derivatives have been tested with UV thermal denaturation studies to determine their effects on an intramolecular triplex DNA (15GCT) at pH 7. In this report, the synthesis and evaluation of triplex stabilization of the target derivative compounds will be discussed.
Purpose
This project focused on synthesizing a group of derivatives that had an expanded ring at the 7,8 position of the flavone backbone. This premise was based on alpha-naphthoflavone to determine if our derivatives displayed similar or greater triplex stabilizing effects.
Results
A total of nine derivatives have been successfully synthesized and purified using the proposed reaction scheme. Those derivatives have been tested against alpha- and beta-naphthoflavone for triplex stabilization. The UV data showed no significant effect of the synthesized derivatives on triplex stabilization.
Significance
Triplex stabilizers can enhance TFO binding to duplex in the anti-gene therapy pathway, which is important for regulation of the central dogma. The significance of this synthesis working is that a similar scheme can also be used to derive other cyclic groups on the flavonoid backbone.
Location
Don and Karen DeRosa University Center (DUC) Poster Hall
Start Date
27-4-2024 10:30 AM
End Date
27-4-2024 12:30 PM
Synthesis and Biophysical Evaluation of 7,8-(Alkylenedioxy)-Flavones
Don and Karen DeRosa University Center (DUC) Poster Hall
Triplex DNA is formed when a third strand, the triplex-forming oligonucleotide (TFO), sequence specifically binds to a duplex. TFOs are considered for anti-gene therapy in which a certain sequence of duplex DNA can be targeted, and triplex formation will regulate the downstream transcription and translation of a mutated protein. However, triplex formation is limited in both thermodynamic and kinetic aspects. Recently, it was found that a flavonoid, quercetin, and its derivatives were able to stabilize triplex DNA without having an effect on duplex DNA. Flavonoids are naturally derived metabolites from plants that have been found to have a variety of roles, including anti-inflammatory, anti-oxidative, anti-bacterial, and anti-carcinogenic effects. From this discovery, a variety of natural flavonoids have been tested against triplex DNA in our lab, and two compounds that stood out were α- and 𝛽- naphthoflavone, which, despite their similarity in structure, only α-naphthoflavone had a significant triplex stabilization effect. Based on this, we designed a synthesis scheme using 7,8-dihydroxyflavone as the starting material for the construction of an aliphatic ring to replace the fused benzene ring in α-naphthoflavone and yield a series of 7,8-(alkylenedioxy)- flavone derivatives. A total of nine derivatives have been synthesized with varying yields and evaluated for purity using NMR. These derivatives have been tested with UV thermal denaturation studies to determine their effects on an intramolecular triplex DNA (15GCT) at pH 7. In this report, the synthesis and evaluation of triplex stabilization of the target derivative compounds will be discussed.
