Identification of Flavone Derivative Displaying a 4'-Aminophenoxy Moiety as Potential Selective Anticancer Agent in NSCLC Tumor Cells

Molecules. 2023 Apr 5;28(7):3239. doi: 10.3390/molecules28073239.

Abstract

Five heterocyclic derivatives were synthesized by functionalization of a flavone nucleus with an aminophenoxy moiety. Their cytotoxicity was investigated in vitro in two models of human non-small cell lung cancer (NSCLC) cells (A549 and NCI-H1975) by using MTT assay and the results compared to those obtained in healthy fibroblasts as a non-malignant cell model. One of the aminophenoxy flavone derivatives (APF-1) was found to be effective at low micromolar concentrations in both lung cancer cell lines with a higher selective index (SI). Flow cytometric analyses showed that APF-1 induced apoptosis and cell cycle arrest in the G2/M phase through the up-regulation of p21 expression. Therefore, the aminophenoxy flavone-based compounds may be promising cancer-selective agents and could serve as a base for further research into the design of flavone-based anticancer drugs.

Keywords: flavone synthesis; non-small cell lung cancer; phenoxy groups; selective anticancer drugs.

MeSH terms

  • A549 Cells
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Apoptosis
  • Carcinoma, Non-Small-Cell Lung* / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Flavones* / pharmacology
  • Flavones* / therapeutic use
  • Humans
  • Lung Neoplasms* / metabolism

Substances

  • Antineoplastic Agents
  • Flavones