Modular Synthetic Approach to Carboranyl‒Biomolecules Conjugates

Area of Science:

• Oncology
• Radiotherapy
• Medicinal Chemistry

Background:

• Boron Neutron Capture Therapy (BNCT) is a promising radiation therapy for cancer.
• Current BNCT agents like l-boronophenylalanine (l-BPA) have limitations in boron content and tumor selectivity.
• Development of novel, tumor-selective, and boron-rich compounds is crucial for advancing BNCT.

Purpose of the Study:

• To design and synthesize novel boron-rich compounds for potential use in BNCT.
• To create a modular strategy for developing agents with enhanced tumor-targeting capabilities.
• To increase boron payload compared to existing BNCT agents.

Main Methods:

• Synthesis of compounds combining *meta*-carborane, a water-soluble monosaccharide, and a linking unit (glycine or ethylenediamine).
• Coupling of synthesized compounds with tumor-selective biomolecules (coumarin derivative and folic acid).
• Characterization of the synthesized boron-rich agents and assessment of their modular design.

Main Results:

• Two novel boron-rich compounds were successfully synthesized.
• The compounds incorporate *meta*-carborane, providing a tenfold increase in boron atoms compared to l-BPA.
• The modular design allows for facile coupling with various tumor-targeting biomolecules, demonstrating feasibility with coumarin and folic acid.

Conclusions:

• A modular and feasible strategy for synthesizing readily obtainable boron-rich agents for BNCT was established.
• The developed compounds offer a significantly higher boron content and potential for improved tumor selectivity.
• These novel agents hold promise for enhanced efficacy in BNCT-based cancer treatment.