Antiproliferative Phenothiazine Hybrids as Novel Apoptosis Inducers against MCF-7 Breast Cancer

Molecules. 2018 May 28;23(6):1288. doi: 10.3390/molecules23061288.

Abstract

We designed a series of novel phenothiazine-1,2,3-triazole hybrids by the molecular hybridization strategy and evaluated their antiproliferative activity against three cancer cell lines (MDA-MB-231, MDA-MB-468 and MCF-7). For the structure-activity relationships, the importance of 1,2,3-triazole and substituents on phenyl ring was explored. Among these phenothiazine-1,2,3-triazole hybrids, compound 9f showed the most potent inhibitory effect against MCF-7 cells, with an IC50 value of 0.8 μM. Importantly, compound 9f could induce apoptosis against MCF-7 cells by regulating apoptosis-related proteins (Bcl-2, Bax, Bad, Parp, and DR5). These potent phenothiazine-1,2,3-triazole hybrids as novel apoptosis inducers might be used as antitumor agents in the future.

Keywords: DR5; MCF-7; apoptosis; phenothiazine-1,2,3-triazole.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Apoptosis Regulatory Proteins / genetics*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drug Screening Assays, Antitumor
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • MCF-7 Cells
  • Molecular Structure
  • Phenothiazines / chemical synthesis*
  • Phenothiazines / chemistry
  • Phenothiazines / pharmacology
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • Phenothiazines