Targeting HER2-Positive HCC1954 Breast Cancer Cells by Novel Thiazole-Dihydrobenzisoxazoles: In-Depth Design, Synthesis and Initial

Background: The most aggressive forms of breast cancer are characterized by independence from steroid hormones but a strong dependence on growth factors. In such cancer cells, oncogenic receptors, including human epidermal growth factor receptor 2 (HER2), are activated, and their targeted inhibition represents an attractive therapeutic strategy. The study aimed to develop small-molecule potential dual heat shock protein 90 (HSP90)-HER2 inhibitors and evaluate them as anticancer agents in HER2-positive cells. Methods: The research project involved obtaining a series of compounds with potential dual inhibitory activity against HSP90 and HER2 by targeted organic synthesis, which was preliminarily assessed using molecular modelling and calculation of key parameters of molecular dynamics. The potential therapeutic benefit of the obtained molecules was studied using basic molecular biological methods, including assessment of cytotoxic activity Results: In this work, novel dual HSP90-HER2 inhibitors, based on the fused thiazole-dihydrobenzisoxazole polycyclic scaffold, were designed and synthesized. The resulting compounds exhibited strong antiproliferative activity against HER2-positive breast cancer cells with high selectivity. Among them, Conclusion: These findings highlight