Synthesis of New Promising BNCT Agents Based on Conjugates of closo-Dodecaborate Anion and Aliphatic Diamino Acids
In this work, a series of boronated amidines based on the <i>closo</i>-dodecaborate anion and amino acids containing an amino group in the side chain of the general formula [B<sub>12</sub>H<sub>11</sub>NHC(NH(CH<sub>2</sub>)<sub>n</sub>CH(NH<sub>3</sub>)COOH)CH<sub>3</sub>], where n = 2, 3, 4, were synthesized. These derivatives contain conserved α-amino and α-carboxyl groups recognized by the binding centers of the large neutral amino acid transporter (LAT) system, which serves as a target for the clinically applied BNCT agent para-boronophenylalanine (BPA). The paper describes several approaches to synthesizing the target compounds, their acute toxicity studies, and tumor uptake studies in vivo in two tumor models. The promising compound [B<sub>12</sub>H<sub>11</sub>NHC(NH(CH<sub>2</sub>)<sub>2</sub>CH(NH<sub>3</sub>)COOH)CH<sub>3</sub>]*3H<sub>2</sub>O demonstrates low toxicity (LD<sub>50</sub> in a range from 150 to 300 mg/kg) and excellent solubility and also shows selective uptake in experimental melanoma in laboratory mice (T/N ratio remained >3 up to 60 min post-injection, with a maximum T/N of 6.2 ± 2.8 at 45 min).
Authors
- Yu. А. Finogenova (ORCID: https://orcid.org/0000-0002-5144-1039)
- К. Yu. Zhizhin (ORCID: https://orcid.org/0000-0002-4475-124X)
- K. E. Shpakova (ORCID: https://orcid.org/0000-0003-0246-1794)
- А. V. Nelyubin (ORCID: https://orcid.org/0000-0002-9990-4231)
- V. А. Skribitsky (ORCID: https://orcid.org/0000-0003-2942-7895)
- Andrey P. Zhdanov (ORCID: https://orcid.org/0000-0003-4083-386X)
- E. Yu. Grigor’eva
- Н. А. Селиванов (ORCID: https://orcid.org/0000-0001-7426-5982)
- A. Yu. Bykov (ORCID: https://orcid.org/0000-0003-1793-8487)
- I. N. Klyukin (ORCID: https://orcid.org/0000-0001-8940-3049)
- А. А. Lipengolts (ORCID: https://orcid.org/0000-0002-5631-9016)
- Alexey S. Kubasov (ORCID: https://orcid.org/0000-0002-0156-5535)
- М. N. Ryabchikova
- Nikolay T. Kuznetsov (ORCID: https://orcid.org/0000-0002-0131-6387)
- Anton Andreevich Kasianov (ORCID: https://orcid.org/0009-0004-0248-9126)
Institutions
- National Research University Higher School of Economics (RU)
- NS Kurnakova Institute of General and Inorganic Chemistry (RU)
- National Research Nuclear University MEPhI (RU)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2024-12-25
- DOI
- https://doi.org/10.3390/ijms26010068
- Citations
- 6
- Primary Topic
- Boron Compounds in Chemistry
- Type
- article
- Field-Weighted Citation Impact
- 2.43
Funders
- Russian Science Foundation
- Russian Academy of Sciences