Licochalcone A-Inspired Chalcones: Synthesis and Their Antiproliferative Potential in Prostate Cancer Cells

Area of Science:

• Medicinal Chemistry
• Oncology
• Natural Products

Background:

• Prostate cancer is a major health concern requiring new therapies.
• Licochalcone A, a natural chalcone, exhibits antiproliferative effects against cancer cells.
• Previous work enhanced curcumin's potency via structural modification.

Purpose of the Study:

• To design and synthesize novel licochalcone A-inspired chalcones.
• To evaluate their antiproliferative activity against prostate cancer models.
• To explore structure-activity relationships for enhanced efficacy.

Main Methods:

• Synthesis via [3,3]-sigmatropic rearrangement and Claisen-Schmidt condensation.
• Antiproliferative activity assessed using WST-1 assay.
• Evaluation in androgen receptor (AR)-positive and AR-null prostate cancer cell lines.

Main Results:

• Licochalcone A showed modest advantage over enzalutamide in 22Rv1 cells.
• Three ester derivatives matched licochalcone A's potency in AR-positive and AR-negative cells.
• Nine derivatives exhibited enhanced selectivity for AR-positive cells (LNCaP, 22Rv1) over AR-negative cells (PC-3, DU145).
• Potency correlated with the R group on the imidazole moiety.

Conclusions:

• The phenol moiety of licochalcone A is a viable target for modification.
• Licochalcone A-inspired chalcones demonstrate potential as anti-prostate cancer agents.
• Further optimization is warranted to develop these compounds into effective therapeutics.