Triazole-based inhibitors for breast cancer: biological activity, SAR and synthetic strategies

Area of Science:

• Medicinal Chemistry
• Drug Discovery
• Oncology

Background:

• Breast cancer presents a significant global health challenge due to its heterogeneity, resistance to therapies, and recurrence.
• Triazole-containing small molecules are increasingly recognized for their chemical stability, favorable pharmacokinetics, and broad biological target engagement in drug discovery.

Purpose of the Study:

• To review the role of triazole scaffolds in breast cancer therapy, encompassing both approved drugs and experimental inhibitors.
• To highlight structure-activity relationships (SAR) and synthetic routes of clinically successful triazole-based drugs.
• To systematically summarize recent advances in triazole-based inhibitors targeting key cancer pathways and discuss their potential for future optimization.

Main Methods:

• Literature review of FDA-approved triazole-based drugs and experimental small molecule inhibitors.
• Systematic summary of recent advances in triazole-based inhibitors targeting specific pathways (aromatase, EGFR, VEGFR-2, CDK4/6, BRAF, PARP-1) and dual targets.
• Critical examination of triazole moieties' ability to overcome challenges like drug resistance, selectivity, and metabolic stability.

Main Results:

• FDA-approved triazole drugs demonstrate successful translation of SAR and synthetic strategies to the clinic.
• Numerous experimental triazole-based inhibitors targeting diverse pathways show significant potential.
• Triazole scaffolds offer advantages in addressing drug resistance, improving selectivity, and enhancing metabolic stability.

Conclusions:

• Triazole-based small molecules represent a valuable class of therapeutics for breast cancer treatment.
• This review provides a framework for designing next-generation triazole-based breast cancer drugs by integrating medicinal chemistry, target biology, and synthetic feasibility.
• Further research into triazole scaffolds can lead to improved therapeutic strategies overcoming current treatment limitations.