In this study, we synthesized novel benzoxazol-2-ylmethyl-(1H-1,2,3-triazol-4-yl)phenyl)-3-aminopropanamides (6a-d) in high yields by means of the Copper-catalysed Azide-Alkyne Cycloaddition (CuAAC) reaction. The synthetic pathway involves the conversion of 2-aminophenol to 2-(bromomethyl)benzoxazole 1, followed by its transformation into the azide derivative 2. Subsequent reaction with functionalized arylalkynes 5a-d under Sharpless’s reaction conditions yields the desired compounds 6a-d. These benzoxazoles were then evaluated as G-Quadruplex DNA (G4) ligands by UV spectroscopy studies using a telomeric sequence (Tel22) as G4 model. We studied how the absorbance at λmax varies over time for the 6a-d/Tel22 mixtures at different molar ratios. Moreover we carried out melting experiments in order to point out any possible stabilization effects arising by ligand interaction. Our findings indicate that Tel22 is slighlty but significantly stabilized by compound 6b at a 1:1 ratio. Furthermore for 6b, these results align well with in silico predictions suggesting that the ligand acts as groove binder interacting with six guanosine residues of the telomeric model.
Design and synthesis of new benzoxazole derivatives and study of their interactions with a G4 model by UV spectroscopy and in silico methods
Giunta, Daniela;Roviello, Giovanni;Solinas, Maurizio
2024
Abstract
In this study, we synthesized novel benzoxazol-2-ylmethyl-(1H-1,2,3-triazol-4-yl)phenyl)-3-aminopropanamides (6a-d) in high yields by means of the Copper-catalysed Azide-Alkyne Cycloaddition (CuAAC) reaction. The synthetic pathway involves the conversion of 2-aminophenol to 2-(bromomethyl)benzoxazole 1, followed by its transformation into the azide derivative 2. Subsequent reaction with functionalized arylalkynes 5a-d under Sharpless’s reaction conditions yields the desired compounds 6a-d. These benzoxazoles were then evaluated as G-Quadruplex DNA (G4) ligands by UV spectroscopy studies using a telomeric sequence (Tel22) as G4 model. We studied how the absorbance at λmax varies over time for the 6a-d/Tel22 mixtures at different molar ratios. Moreover we carried out melting experiments in order to point out any possible stabilization effects arising by ligand interaction. Our findings indicate that Tel22 is slighlty but significantly stabilized by compound 6b at a 1:1 ratio. Furthermore for 6b, these results align well with in silico predictions suggesting that the ligand acts as groove binder interacting with six guanosine residues of the telomeric model.File | Dimensione | Formato | |
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Journal of Molecular Liquids 410 (2024) 125491.pdf
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Descrizione: Design and synthesis of new benzoxazole derivatives and study of their interactions with a G4 model by UV spectroscopy and in silico methods
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