Compounds having heat shock heat protein 70 inhibitory activity and applications thereof

Abstract

The invention belongs to the technical field of medicine, and specifically provides compounds with heat shock protein 70 inhibitory activity and applications thereof. The compound includes at least one of the three compounds in the specification. The compound of the present invention has weak response ability to glutathione and strong binding ability to heat shock protein 70, and has high activity and low side effect in complex biological system, so it can be used as an inhibitor.

Description

technical field [0001] The invention belongs to the technical field of medicine, in particular to a compound with heat shock protein 70 inhibitory activity and application thereof. Background technique [0002] Heat shock protein 70 (Hsp70) is widely distributed in various organisms, and its sequence and structure are highly conserved from lower bacteria to higher mammals. Hsp70 consists of an amino-terminal nucleotide-binding domain, a carboxy-terminal substrate-binding domain (SBD), and a hydrophobic flexible chain of about ten amino acid residues connecting between the nucleotide-binding domain and the substrate-binding domain. Among them, the substrate-binding domain (SBD) can be further divided into β-sheet-rich SBDβ subdomain and α-helix-rich SBDα subdomain. [0003] There are literature reports, (PES) is an inhibitor of Hsp70 and is thought to possibly bind to the SBD of Hsp70. PES can selectively kill tumor cells, but has no toxicity to normal cells at the same c...

AI Technical Summary

Problems solved by technology

PES can selectively kill tumor cells, but has no toxicity to normal cells at the same concentration, and can inhibit the activity of tumor cells such as leukemia, lymphoma, bladder cancer, pancreatic cancer, non-small cell lung cancer, and cervical cancer. Glutathione (GSH), which exists in large quantities in the body, also has strong responsiveness, so it is necessary to develop inhibitors that have weak responsiveness to GSH and maintain or improve the binding ability to Hsp70, so as to improve the activity of compounds in complex biological systems and reduce possible side effects

Images