In vitro anti-breast cancer study of hybrid cinnamic acid derivatives bearing 2-thiohydantoin moiety

Future Med Chem. 2024 Aug 17;16(16):1665-1684. doi: 10.1080/17568919.2024.2366694. Epub 2024 Jul 1.

Abstract

Aim: To synthesize new hybrid cinnamic acids (10a, 10b and 11) and ester derivatives (7, 8 and 9) and investigate their anti-breast cancer activities.Materials & methods: Compounds 7-11 were evaluated (in vitro) for their cytotoxic activities against the MCF-7 cell line. A flow cytometry examination was performed. Protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2), topoisomerase II and caspase-9 were measured by qRT-PCR. Molecular docking studies were conducted.Results: Several components were discovered to be active, mainly component 11, which induced arrest in the cell cycle at phase S, greatly decreased the expression of Nrf2 and topoisomerase II; and upregulated the expression of caspase-9.Conclusion: The newly thiohydantoin-cinnamic acid hybrids can contribute to creating promising candidates for cancer drugs.

Keywords: 2-thiohydantoin; Nrf2; anti-breast cancer; caspase-9; cinnamic acid and ester derivatives; topoisomerase II.

Plain language summary

[Box: see text].

MeSH terms

  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Apoptosis / drug effects
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Caspase 9 / metabolism
  • Cell Proliferation / drug effects
  • Cinnamates* / chemical synthesis
  • Cinnamates* / chemistry
  • Cinnamates* / pharmacology
  • DNA Topoisomerases, Type II / metabolism
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • MCF-7 Cells
  • Molecular Docking Simulation*
  • Molecular Structure
  • NF-E2-Related Factor 2 / antagonists & inhibitors
  • NF-E2-Related Factor 2 / metabolism
  • Structure-Activity Relationship
  • Thiohydantoins / chemical synthesis
  • Thiohydantoins / chemistry
  • Thiohydantoins / pharmacology

Substances

  • Cinnamates
  • cinnamic acid
  • Antineoplastic Agents
  • Thiohydantoins
  • NF-E2-Related Factor 2
  • DNA Topoisomerases, Type II
  • NFE2L2 protein, human
  • Caspase 9