Novel O-acylated (E)-3-aryl-6,7-dihydrobenzisoxazol-4(5H)-one oximes targeting HSP90-HER2 axis in breast cancer cells.

Autor: Piven YA; Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Akad. Kuprevicha st. 5/2, Minsk 220141, Belarus., Yastrebova MA; Institute of Gene Biology, Russian Academy of Sciences, Moscow, Vavilova st. 34/5, Moscow 119334, Russian Federation., Khamidullina AI; Institute of Gene Biology, Russian Academy of Sciences, Moscow, Vavilova st. 34/5, Moscow 119334, Russian Federation., Scherbakov AM; Department of Experimental Tumor Biology, Blokhin N.N. National Medical Research Center of Oncology, Kashirskoye sh. 24, Moscow 115522, Russian Federation., Tatarskiy VV; Institute of Gene Biology, Russian Academy of Sciences, Moscow, Vavilova st. 34/5, Moscow 119334, Russian Federation., Rusanova JA; Taras Shevchenko National University of Kyiv, 64/13, Volodymyrska str., Kyiv 01601, Ukraine., Baranovsky AV; Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Akad. Kuprevicha st. 5/2, Minsk 220141, Belarus., Zinovich VG; Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Akad. Kuprevicha st. 5/2, Minsk 220141, Belarus., Khlebnicova TS; Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Akad. Kuprevicha st. 5/2, Minsk 220141, Belarus., Lakhvich FA; Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Akad. Kuprevicha st. 5/2, Minsk 220141, Belarus.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2022 Jan 01; Vol. 53, pp. 116521. Date of Electronic Publication: 2021 Nov 22.
DOI: 10.1016/j.bmc.2021.116521
Abstrakt: Novel O-acylated (E)-3-aryl-6,7-dihydrobenzisoxazol-4(5H)-one oximes were designed as potential HSP90 inhibitors. A series of the compounds was synthesized by oximation of (E)-3-aryl-6,7-dihydrobenzisoxazol-4(5H)-ones followed by O-acylation with acylamidobenzoic acids. The obtained compounds showed an antiproliferative effect on three breast cancer cell lines (MCF7, MDA-MB-231 and HCC1954). Compound 16s exhibited high antiproliferative potency against HCC1954 breast cancer cells with the IC 50 value of 6 µM was selected for in-depth evaluation. Compound 16s did not inhibit the growth of normal epithelial cells. We have demonstrated that the compound 16s can induce apoptosis in cancer cells via inhibition of HSP90 "client" proteins including a key oncogenic receptor, HER2/neu. Described here compounds can be considered for further basic and preclinical investigation as a part of HSP90/HER2-targeted therapies.
(Copyright © 2021 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: