Curcumin-derived functionalized thiazepanes to selectively target colon cancer cells

01 November 2022 → 31 October 2024
Research Foundation - Flanders (FWO)
Research disciplines
  • Medical and health sciences
    • Medical biochemistry and metabolism not elsewhere classified
    • Cancer therapy
    • Compound screening
    • In vitro testing
    • Medicinal products not elsewhere classified
Curcumin(oid) selectivity Intracellular accumulation and metabolism Colon cancer in vitro model
Project description

Since cancer is the second cause of death worldwide, the search for effective therapy without side effects is pertinent. To this end, selective targeting of cancer cells compared to surrounding healthy tissue is a main strategy. We have recently demonstrated that the metabolism and accumulation pattern of phenolics is deviating in dysfunctional compared to healthy cells. In this scope, the distinct cellular fate in dysfunctional (cancer) cells may offer an alternative approach for selective anticancer targeting. Curcumin is a polyphenol extracted from Curcuma longa with several beneficial properties including anticancer activity. However, its low bioavailability, stability and PAINS classification hamper application in health care. Previously, 90 curcumin analogues have been synthesized in our lab, including thiazepane derivatives which deviate from the curcumin structure by their out-of-plane configuration. In this project, the most promising analogues will be investigated using 3D in vitro models for colon cancer, more specifically tumour spheroids and a newly developed embedded tumour model. This way, the analogues can be screened for selectivity by examining accumulation, biotransformation and -activity in one model using microscopic, analytical (UPLC-QTOF-MS), cellular and molecular techniques, followed by in vivo validation. The new compounds and mechanistic insights may therefore open perspectives for product development in food (supplement) and pharma industry.