Amonafide-based H₂O₂-responsive theranostic prodrugs: Exploring the correlation between H₂O₂ level and anticancer...

Area of Science:

• Medicinal Chemistry
• Oncology
• Biochemistry

Background:

• Hydrogen peroxide (H2O2)-activated prodrugs offer targeted anticancer therapy by exploiting elevated H2O2 levels in cancer cells.
• The efficacy of H2O2-activated prodrugs varies with intracellular H2O2 concentrations across different cancer types.

Purpose of the Study:

• To develop a novel H2O2-activated theranostic prodrug for enhanced cancer treatment.
• To evaluate the efficacy and selectivity of the developed prodrug in cancer cell lines.

Main Methods:

• Development of PBE-AMF and PBA-AMF prodrugs.
• In vitro assays using MDA-MB-231 (breast cancer) and MCF-10A (non-cancerous) cell lines.
• Mechanistic studies including DNA synthesis, ATP level, apoptosis, and cell cycle analysis.

Main Results:

• PBE-AMF showed a positive correlation between H2O2 levels and anticancer activity, with MDA-MB-231 cells being most susceptible.
• PBA-AMF demonstrated improved stability, solubility, and selective inhibition of MDA-MB-231 cell proliferation.
• PBA-AMF induced apoptosis and cell cycle arrest by inhibiting DNA synthesis and reducing ATP levels.

Conclusions:

• PBA-AMF is a potent and selective theranostic prodrug for targeting cancer cells with high H2O2 levels.
• This novel prodrug broadens the scope of H2O2-activated anticancer agents.
• PBA-AMF holds promise for broader applications in cancer diagnostics and treatment, as well as other diseases associated with elevated H2O2.