Novel Chrysin-De-Allyl PAC-1 Hybrid Analogues as Anticancer Compounds: Design, Synthesis, and Biological Evaluation

Molecules. 2020 Jul 4;25(13):3063. doi: 10.3390/molecules25133063.

Abstract

New chrysin-De-allyl-Pac-1 hybrid analogues, tethered with variable heterocyclic systems (4a-4o), were rationally designed and synthesized. The target compounds were screened for in vitro antiproliferative efficacy in the triple-negative breast cancer (TNBC) cell line, MDA-MB-231, and normal human mammary epithelial cells (HMECs). Two compounds, 4g and 4i, had the highest efficacy and selectivity towards MDA-MB-231 cells, and thus, were further evaluated by mechanistic experiments. The results indicated that both compounds 4g and 4i induced apoptosis by (1) inducing cell cycle arrest at the G2 phase in MDA-MB-231 cells, and (2) activating the intrinsic apoptotic pathways in a concentration-dependent manner. Physicochemical characterizations of these compounds suggested that they can be further optimized as potential anticancer compounds for TNBC cells. Overall, our results suggest that 4g and 4i could be suitable leads for developing novel compounds to treat TNBC.

Keywords: anticancer compounds; chrysin analogues; cytotoxicity; flavonoid; triple-negative breast cancer.

MeSH terms

  • Allyl Compounds / chemistry*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Cell Cycle
  • Cell Movement
  • Cell Proliferation
  • Female
  • Flavonoids / chemistry*
  • Humans
  • Hydrazones / chemistry*
  • Piperazines / chemistry*
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / pathology
  • Tumor Cells, Cultured

Substances

  • (4-benzylpiperazin-1-yl)acetic acid (3-allyl-2-hydroxybenzylidene)hydrazine
  • Allyl Compounds
  • Antineoplastic Agents
  • Flavonoids
  • Hydrazones
  • Piperazines
  • chrysin