Design, synthesis, and anti-gastric cancer activity of novel 2,5-diketopiperazine

Abstract Over the past decades, anti-cancer drugs consist of cytotoxic drugs have been interested and developed. Despite the great advances in chemotherapy, there is still no certain medical treatment for cancer. During this investigation, a novel 2,5-diketopiperazine derivative 3(R),6(S)-bis (4-hydroxy phenyl)-piperazine-2,5-dione: (BHPPD) was designed, synthesized, and evaluated. The effects on intestinal protease consist of conformation, activity, and cytotoxic effect on cancer cell lines by the various methods were assessed. The binding interaction between BHPPD with α-Chymotrypsin (α-Chy) has been described utilizing many spectroscopic and computational approaches. Intrinsic fluorescence analyses exhibited static quenching as the primary quenching mod in α-Chy–BHPPD interaction, which is further confirmed by UV–vis analyses. Likewise, binding and thermodynamic constants are estimated from temperature dependent fluorescence results. Furthermore, structural alterations of the enzyme upon binding with BHPPD were presented by circular dichroism (CD) analyses. The Molecular docking assessment presented the specific binding microenvironment of BHPPD in α-Chy. Besides with this research, molecular dynamics Simulation is performed to estimate the stability of α-Chy, α-Chy–BHPPD system. These results showed the vigorous binding affinity of the drug with intestinal protease. MTT analysis of BHPPD represented high cytotoxic effect against AGS cell line compared to normal cell line. Quantitative analysis shows that BHPPD treatment significantly increased the expression of caspase3, 9, and 8 genes and decreased GR expression in AGS cell line. Our team hopes that the results of this research will be useful for medical science and pharmacy.

• Publication year

  2019

• Venue

  Journal of Molecular Liquids

• Publication date

  2019-08-20

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1016/J.MOLLIQ.2019.111585
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

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