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• W2078550165 abstract "HSP70 is a potential target for tumour treatment. HSP70 plays significant roles in several biological processes, including the regulation of apoptosis. In this study, piperidine derivatives were designed as novel HSP70 inhibitors based on virtual fragment screening performed in Dock 4.0, Discovery Studio 2.5 and SYBYL 6.9. A total of 67 novel piperidine derivatives were synthesized. Cell viability assays were performed in 16 cancer cell lines. The emphasis was placed on lapatinib-resistant breast cancer cells (BT/Lap(R)1.0, MDA-MB-361, SK/Lap(R)1.0, and MDA-MB-453). The compounds HSP70-36/37/40/43/46 significantly inhibited the proliferation of human breast cancer cells. Compound HSP70-36 inhibited the growth of BT474 and BT/Lap(R)1.0 cells with IC50 values of 1.41 μM and 1.47 μM, respectively. The binding affinity of HSP70-36/HSP70 was evaluated by surface plasmon resonance and yielded Kd values of 2.46 μM. The LD50 was 869.0 mgkg(-1). These data suggest that HSP70-36 may be a potential candidate compound for tumour treatment." @default.
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• W2078550165 date "2015-06-01" @default.
• W2078550165 modified "2023-10-14" @default.
• W2078550165 title "Design and synthesis of piperidine derivatives as novel human heat shock protein 70 inhibitors for the treatment of drug-resistant tumors" @default.
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• W2078550165 doi "https://doi.org/10.1016/j.ejmech.2015.04.043" @default.
• W2078550165 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25935385" @default.
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