TY - JOUR

T1 - Nido-Carborane Derivatives of (S)-Ornithine and (S)-Lysine as Potential Boron Delivery Agents

T2 - Synthesis and In Vitro Evaluation

AU - Gruzdev, Dmitry A

AU - Levit, Galina L

AU - Musiyak, Vera V

AU - Telegina, Angelina A

AU - Ganebnykh, Ilya N

AU - Ezhikova, Marina A

AU - Kodess, Mikhail I

AU - Solovieva, Olga I

AU - Gusel'nikova, Tatiana Y

AU - Razumov, Ivan A

AU - Krasnov, Victor P

N1 - This research was financially supported by the Ministry of Science and Higher Education of the Russian Federation (theme no. 124020200038-6 in part of the compounds synthesis and no. 124020500023-9 in part of in vitro evaluation).

PY - 2025/9/3

Y1 - 2025/9/3

N2 - 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 (S)-ornithine and (S)-lysine derivatives containing a 7,8-dicarba-nido-undecaborane (nido-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 nido-carborane residue in the side chain. It has been found that sodium salt of Nε-(nido-carboran-7-yl)acetyl-(S)-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 (S)-lysine derivative containing a nido-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.

AB - 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 (S)-ornithine and (S)-lysine derivatives containing a 7,8-dicarba-nido-undecaborane (nido-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 nido-carborane residue in the side chain. It has been found that sodium salt of Nε-(nido-carboran-7-yl)acetyl-(S)-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 (S)-lysine derivative containing a nido-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.

KW - Humans

KW - Lysine/chemistry

KW - Cell Line, Tumor

KW - Ornithine/chemistry

KW - Boron Neutron Capture Therapy/methods

KW - Boron/chemistry

KW - Boron Compounds/chemistry

KW - Boranes/chemistry

KW - Cell Survival/drug effects

UR - https://www.scopus.com/pages/publications/105015894456

U2 - 10.3390/ijms26178560

DO - 10.3390/ijms26178560

M3 - Article

C2 - 40943478

VL - 26

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 17

M1 - 8560

ER -