27049-45-2Relevant articles and documents
Phenyl-1-Pyridin-2yl-Ethanone-Based Iron Chelators Increase IκB-α Expression, modulate CDK2 and CDK9 activities, and inhibit HIV-1 transcription
Kumari, Namita,Iordanskiy, Sergey,Kovalskyy, Dmytro,Breuer, Denitra,Niu, Xiaomei,Lin, Xionghao,Xu, Min,Gavrilenko, Konstantin,Kashanchi, Fatah,Dhawan, Subhash,Nekhai, Sergei
, p. 6558 - 6571 (2014)
HIV-1 transcription is activated by the Tat protein, which recruits CDK9/cyclin T1 to the HIV-1 promoter. CDK9 is phosphorylated by CDK2, which facilitates formation of the high-molecular-weight positive transcription elongation factor b (P-TEFb) complex. We previously showed that chelation of intracellular iron inhibits CDK2 and CDK9 activities and suppresses HIV-1 transcription, but the mechanism of the inhibition was not understood. In the present study, we tested a set of novel iron chelators for the ability to inhibit HIV-1 transcription and elucidated their mechanism of action. Novel phenyl-1-pyridin-2yl-ethanone (PPY)-based iron chelators were synthesized and examined for their effects on cellular iron, HIV-1 inhibition, and cytotoxicity. Activities of CDK2 and CDK9, expression of CDK9-dependent and CDK2-inhibitory mRNAs, NF-κB expression, and HIV-1- and NF-κB-dependent transcription were determined. PPY-based iron chelators significantly inhibited HIV-1, with minimal cytotoxicity, in cultured and primary cells chronically or acutely infected with HIV-1 subtype B, but they had less of an effect on HIV-1 subtype C. Iron chelators upregulated the expression of IκB-α, with increased accumulation of cytoplasmic NF- κB. The iron chelators inhibited CDK2 activity and reduced the amount of CDK9/cyclin T1 in the large P-TEFb complex. Iron chelators reduced HIV-1 Gag and Env mRNA synthesis but had no effect on HIV-1 reverse transcription. In addition, iron chelators moderately inhibited basal HIV-1 transcription, equally affecting HIV-1 and Sp1- or NF-κB-driven transcription. By virtue of their involvement in targeting several key steps in HIV-1 transcription, these novel iron chelators have the potential for the development of new therapeutics for the treatment of HIV-1 infection.
Site-Selective Pd-Catalyzed C(sp3)?H Arylation of Heteroaromatic Ketones
Kudashev, Anton,Baudoin, Olivier
supporting information, p. 17688 - 17694 (2021/11/16)
A ligand-controlled site-selective C(sp3)?H arylation of heteroaromatic ketones has been developed using Pd catalysis. The reaction occurred selectively at the α- or β-position of the ketone side-chain. The switch from α- to β-arylation was realized by addition of a pyridone ligand. The α-arylation process showed broad scope and high site- and chemoselectivity, whereas the β-arylation was more limited. Mechanistic investigations suggested that α-arylation occurs through C?H activation/oxidative addition/reductive elimination whereas β-arylation involves desaturation and aryl insertion.
Thiazole-based Orange-emitting Excited-State Intramolecular Proton Transfer Chemosensors for Selective and Ratiometric Sensing of Zn2+ Ions
Kim, Sangho,Somasundaram, Sivaraman,Park, Sanghyuk
supporting information, p. 937 - 938 (2019/10/22)
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