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trans-Styrylquinazolinone CYP1B1 inhibitors as potential therapeutics in A549 cells

Jiajing Cai1, Fengyuan Yang2, Meixian Yang1

  • 1Department of Radiation Medicine, College of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, China.

European Journal of Medicinal Chemistry
|August 6, 2025
PubMed

Insights

Researchers developed novel trans-styrylquinazolinone inhibitors targeting Cytochrome CYP1B1 (a protein linked to cancer and drug resistance). These compounds show significant potential in overcoming tumor drug resistance and inhibiting cancer cell invasion and migration.

Area of Science:

  • Medicinal Chemistry
  • Pharmacology
  • Oncology

Background:

  • Cytochrome CYP1B1 contributes to tumorigenesis by activating carcinogens and estrogens.
  • Overexpression of CYP1B1 in hormone-related tumors leads to anticancer drug resistance.
  • Selective inhibition of CYP1B1 is a promising strategy to overcome tumor drug resistance.

Purpose of the Study:

  • To design and synthesize novel trans-styrylquinazolinone derivatives as selective CYP1B1 inhibitors.
  • To optimize the inhibitory activity and physicochemical properties of these compounds.
  • To evaluate their potential in reversing drug resistance and inhibiting cancer cell invasion and migration.

Main Methods:

  • Synthesis of 46 trans-styrylquinazolinone derivatives.
  • Enzyme inhibition assays (7-Ethoxyresorufin-O-deethylase screening) to determine IC50 values.
  • Molecular docking to investigate binding interactions with CYP1B1.
  • A549 cell-based assays to assess reversal of paclitaxel resistance and inhibition of invasion/migration.

Main Results:

  • One trans-styrylquinazolinone derivative showed potent CYP1B1 inhibition with an IC50 of 6.75 × 10^-3 nM.
  • Optimization led to 2-styrylquinazolin-4-amine derivatives with greatly improved inhibitory activity (IC50 = 6.05 × 10^-6 nM).
  • Three compounds demonstrated significant reversal of paclitaxel resistance and inhibited cancer cell invasion and migration in A549 cells.

Conclusions:

  • Trans-styrylquinazolinone derivatives are effective inhibitors of Cytochrome CYP1B1.
  • These compounds show potential for overcoming drug resistance in hormone-related tumors.
  • The developed inhibitors exhibit promising applications in cancer prevention and treatment by inhibiting invasion and migration.

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