Novel <i>N</i>-(4,5,6,7-tetrahydrobenzisoxazol-4-yl)amides as HSP90 inhibitors: design, synthesis and biological evaluation.

ABSTRACT: Novel N-(4,5,6,7-tetrahydrobenzisoxazol-4-yl)amide derivatives were designed and synthesized as potential HSP90 inhibitors. The synthetic pathway commenced with 6,7-dihydrobenzo[d]isoxazol-4(5H)-ones, utilizing the Ritter reaction as a key step. Molecular docking, molecular dynamics simulations, and MM/GBSA analysis guided the selection of compounds for synthesis and provided insights into the interaction mode of the most active compound with HSP90α. The synthesized compounds exhibited significant antiproliferative effects against breast cancer cell lines ERα+ MCF7 and HER2+ HCC1954. Lead compounds with submicromolar IC₅₀ values, initially synthesized as racemates, were subsequently obtained and tested in their enantiopure forms. In HER2+ HCC1954 cancer cell

SUBMITTER: Varabyeva NA 

PROVIDER: S-EPMC11987037 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature