Nido-Carborane Derivatives of (S)-Ornithine and (S)-Lysine as Potential Boron Delivery Agents: Synthesis and In Vitro Evaluation

Derivatives of natural amino acids are selectively absorbed by many types of tumour cells. This makes the use of amino acids, especially polyfunctional ones, attractive as a basis in the design of low-toxicity agents for targeted boron delivery for boron neutron capture therapy (BNCT) of tumours. We synthesized a series of new (<i>S</i>)-ornithine and (<i>S</i>)-lysine derivatives containing a 7,8-dicarba-<i>nido</i>-undecaborane (<i>nido</i>-carborane) residue attached to the amino group in the side chain or alpha position. The MTT assay demonstrated moderate cytotoxicity of the lysine and ornithine derivatives containing a <i>nido</i>-carborane residue in the side chain. It has been found that sodium salt of <i>N</i>^ε-(<i>nido</i>-carboran-7-yl)acetyl-(<i>S</i>)-lysine is capable of accumulation by MDA-MB-231 (human breast carcinoma) and SK-Mel 28 (human melanoma) cell lines, providing a boron concentration of up to 0.67 µg/10⁶ cells in in vitro experiments. This (<i>S</i>)-lysine derivative containing a <i>nido</i>-carborane residue in the side chain can be considered as a promising compound for in-depth study in vivo experiments aimed at designing an efficient boron delivery agent for BNCT.