136616-34-7Relevant articles and documents
Discovery of novel anti-breast cancer agents derived from deguelin as inhibitors of heat shock protein 90 (HSP90)
Ann, Jihyae,Byun, Woong Sub,Kim, Ji Young,Kim, Yoon-Jae,Lee, Jeewoo,Lee, Sangkook,Nam, Gibeom,Nguyen, Cong-Truong,Park, Hyun-Ju,Park, Soeun,Sahu, Raghaba,Seo, Jae Hong
, (2020/07/15)
A series of O-substituted analogues of the B,C-ring truncated scaffold of deguelin were designed as C-terminal inhibitors of heat shock protein 90 (HSP90) and investigated as novel antiproliferative agents against HER2-positive breast cancer. Among the synthesized compounds, compound 80 exhibited significant inhibition in both trastuzumab-sensitive and trastuzumab-resistant breast cancer cells, whereas compound 80 did not show any cytotoxicity in normal cells. Compound 80 markedly downregulated the expression of the major client proteins of HSP90 in both cell types, indicating that the cytotoxicity of 80 in breast cancer cells is attributed to the destabilization and inactivation of HSP90 client proteins and that HSP90 inhibition represents a promising strategy to overcome trastuzumab resistance. A molecular docking study of 80 with the homology model of a HSP90 homodimer showed that 80 fit nicely in the C-terminal domain with a higher electrostatic complementary score than that of ATP.
Topologically Controlled Coulombic Interactions, a New Tool in the Developing of Novel Reactivity. Photochemical and Electrochemical Cleavage of Phenyl Alkyl Ethers
Marquet, Jorge,Cayon, Eduard,Martin, Xavier,Casado, Francisco,Gallardo, Iluminada,et al.
, p. 3814 - 3825 (2007/10/02)
The hypothesis that a specific placement of a positive charge would dramatically alter the behavior of a charged intermediate has been tested.Phenyl ethers substituted by electron-attracting groups do not undergo reductive fragmentation.However, related α-piperidino-ω-(4-substituted-phenoxy)alkanes give alkyl ether photocleavage when the linker between the redox centers is short, or the usual substitution-reduction photochemistry when it is long.Mechanistic experiments suggest that the photofragmentation process operates through space intramolecular electron transfer to the triplet aromatic chromophore and that a coplanar relative orientation of the alkyl ether bond and the phenyl ring is compulsory for the photofragmentation to be observed.Configuration interaction AM1 calculations justify the described facts, indicating that the fragmentation process is only operative when a Coulombic stabilization of a ?* intramolecular electron transfer excited state is produced.Electrochemical studies carried out with the corresponding quaternary salts (intermolecular generation of the phenyl ether radical anion) confirm the conclusions derived from the photochemical experiments.
