21332-92-3Relevant academic research and scientific papers
Spectroscopy and photophysics of monomethyl-substituted derivatives of 5-deazaalloxazine and 10-ethyl-5-deaza-isoalloxazine
Pruka?a, Dorota,Taczkowska, Magdalena,Gierszewski, Mateusz,P?dziński, Tomasz,Sikorski, Marek
, p. 505 - 521 (2014)
Steady-state and time-resolved spectra were used to describe the singlet and triplet states of 8-methyl-5-deazaalloxazine (8-Me-5-DAll), 9-methyl-5-deazaalloxazine (9-Me-5-DAll) and 10-ethyl-5-deaza-isoalloxazine (10-Et-5-DIAll). Solvatochromic properties were described using different polarity scales, including Δf and the four-parameter scale proposed by Catala?n. The results indicate that the Catala?n scale shows a strong influence of solvent acidity (hydrogen-bond donating ability) on the emission properties of 8-Me-5-DAll and 9-Me-5-DAll. These results indicate the importance of intermolecular solute-solvent hydrogen-bonding interactions in the excited state of these compounds. Contrary to deazaalloxazines, solvent acidity affects the absorption spectra of 10-Et-5-DIAll. Fluorescence lifetimes and quantum yields and also transient absorption spectra were determined for all of the compounds studied. Electronic structure and S 0 -S i, S 0 -T i, T 1 -T i transitions energies and oscillator strengths were calculated using the TD-DFT methods. Theoretical calculations were compared to experimental data.
5-Deazaflavin derivatives as inhibitors of p53 ubiquitination by HDM2
Dickens, Michael P.,Roxburgh, Patricia,Hock, Andreas,Mezna, Mokdad,Kellam, Barrie,Vousden, Karen H.,Fischer, Peter M.
, p. 6868 - 6877 (2013/11/06)
Based on previous reports of certain 5-deazaflavin derivatives being capable of activating the tumour suppressor p53 in cancer cells through inhibition of the p53-specific ubiquitin E3 ligase HDM2, we have conducted an structure-activity relationship (SAR) analysis through systematic modification of the 5-deazaflavin template. This analysis shows that HDM2-inhibitory activity depends on a combination of factors. The most active compounds (e.g., 15) contain a trifluoromethyl or chloro substituent at the deazaflavin C9 position and this activity depends to a large extent on the presence of at least one additional halogen or methyl substituent of the phenyl group at N10. Our SAR results, in combination with the HDM2 RING domain receptor recognition model we present, form the basis for the design of drug-like and potent activators of p53 for potential cancer therapy.
