Dual-target carbonic anhydrase inhibitors in cancer therapy: progress, challenges, and opportunities

Area of Science:

• Biochemistry
• Pharmacology
• Medicinal Chemistry

Background:

• Carbonic anhydrases (CA) are crucial metalloenzymes regulating physiological processes like pH and metabolism.
• Current carbonic anhydrase inhibitors (CAIs) face challenges including toxicity, drug resistance, and limited efficacy in complex diseases.
• Multi-target combination therapy, especially dual-target agents, presents a promising approach to enhance therapeutic outcomes.

Purpose of the Study:

• To review recent advancements in dual-target carbonic anhydrase inhibitors (CAIs).
• To highlight design strategies and structure-activity relationships (SAR) of novel CAIs.
• To discuss translational challenges and future perspectives for CA-directed therapies.

Main Methods:

• Literature review focusing on dual-target CAIs.
• Analysis of design strategies and SAR data.
• Discussion of clinical translation and future research directions.

Main Results:

• Dual-target CAIs show potential to overcome limitations of single-target inhibitors.
• Synergistic interactions between CA and targets like EGFR, VEGFR, and HDAC are key design considerations.
• Progress in SAR studies informs the development of more effective CAIs.

Conclusions:

• Dual-target CAIs represent a significant advancement in carbonic anhydrase-directed therapies.
• Further research into design, SAR, and translational aspects is crucial for clinical success.
• Next-generation CAIs hold promise for treating multifactorial diseases with improved efficacy and reduced toxicity.