Coumarin Derivatives as Anticancer Agents: Mechanistic Landscape with an Emphasis on Breast Cancer

Area of Science:

• Medicinal Chemistry
• Pharmacology
• Oncology

Background:

• Coumarin derivatives are a versatile chemotype with demonstrated anticancer properties.
• Existing research highlights their potential across various cancer types, including breast, lung, prostate, and colorectal cancers.

Purpose of the Study:

• To review and synthesize recent in vitro and in vivo evidence on coumarin-based scaffolds for anticancer applications.
• To summarize major mechanisms of action, highlight key chemotypes, and discuss structure-activity relationships.
• To identify translational gaps and outline priorities for preclinical optimization of coumarin derivatives.

Main Methods:

• Narrative review of published in vitro and in vivo studies on coumarin derivatives.
• Analysis of mechanisms of action, including apoptosis induction, signaling pathway modulation, and drug resistance.
• Comparison of coumarin derivative potency and selectivity across different cancer cell lines and models.

Main Results:

• Coumarins exhibit diverse anticancer mechanisms, including apoptosis induction, PI3K/Akt/mTOR signaling modulation, anti-angiogenesis, and overcoming multidrug resistance.
• Specific chemotypes like benzimidazoles, triazoles, and furocoumarins show promise, with structure-activity trends identified.
• Translational challenges include selectivity, pharmacokinetics, and safety; preclinical optimization is needed.

Conclusions:

• Coumarin derivatives are adaptable, multi-target anticancer leads, especially for hormone-dependent breast cancer.
• Further preclinical optimization focusing on target selection, combination therapies, and pharmacokinetic profiling is crucial for clinical translation.
• Coumarins remain relevant for various other tumor types beyond breast cancer.