ABSTRACT
Herein, a series of new isatin derivatives was designed and synthesized (1-9) as broad-spectrum antiviral agents. Consequently, the antiviral activities of the synthesized compounds (1-9) were pursued against three viruses, namely influenza virus (H1N1), herpes simplex virus 1 (HSV-1), and coxsackievirus B3 (COX-B3). In particular, compounds 9, 5, and 4 displayed the highest antiviral activity against H1N1, HSV-1, and COX-B3 with IC50 values of 0.0027, 0.0022, and 0.0092 µM, respectively. Compound 7 was the safest, with a CC50 value of 315,578.68 µM. Moreover, a quantitative PCR (real-time PCR) assay was carried out for the most relevant compounds. The selected compounds exhibited a decrease in viral gene expression. Additionally, the conducted in silico studies emphasized the binding affinities of the synthesized compounds and their reliable pharmacokinetic properties as well. Finally, a structure-antiviral activity relationship study was conducted to anticipate the antiviral activity change upon future structural modification.
ABSTRACT
Breslow intermediates that bear radical-stabilizing Nâ substituents, such as benzyl, cinnamyl, and diarylmethyl, undergo facile homolytic C-N bond scission under mild conditions to give products of formal [1,3]â rearrangement rather than benzoin condensation. EPR experiments and computational analysis support a radical-based mechanism. Implications for thiamine-based enzymes are discussed.
Subject(s)
Alcohols/chemical synthesis , Thiamine/chemical synthesis , Alcohols/chemistry , Carboxy-Lyases/chemistry , Carboxy-Lyases/metabolism , Free Radicals/chemical synthesis , Free Radicals/chemistry , Molecular Structure , Quantum Theory , Thiamine/chemistryABSTRACT
A novel Claisen rearrangement in which the Breslow intermediate is engaged as a hydroxy-substituted N,S-ketene acetal to provide complex 3° alcohols without the use of organometallic reagents is reported. The reaction constitutes an unprecedented reactivity mode for the Breslow intermediate.
