ABSTRACT
A new group of charge-compensated nido-carboranyl derivatives of sulfur-containing amino acids and biotin has been synthesized in which the boron atom in position 9 or 10 of carborane is attached to a positively charged sulfur atom. The possibilities of obtaining symmetrical B(10)-substituted and asymmetric B(9)-substituted nido-carboranes were studied. Using the example of (S)-methionine and D-biotin derivatives, water-soluble S-substituted charge-compensated nido-carboranes with free functional groups were prepared. The results obtained open up prospects for the development of potential boron delivery agents for BNCT as well as new bioactive compounds containing a negatively charged nido-carboranyl fragment bearing a positive charge on the sulfur atom associated with the boron cluster.
ABSTRACT
The design of highly selective low-toxic, low-molecular weight agents for boron delivery to tumour cells is of decisive importance for the development of boron neutron capture therapy (BNCT), a modern efficient combined method for cancer treatment. In this work, we developed a simple method for the preparation of new closo- and nido-carborane-containing folic acid bis-amides containing 18-20 boron atoms per molecule. Folic acid derivatives containing nido-carborane residues were characterised by high water solubility, low cytotoxicity, and demonstrated a good ability to deliver boron to tumour cells in in vitro experiments (up to 7.0 µg B/106 cells in the case of U87 MG human glioblastoma cells). The results obtained demonstrate the high potential of folic acid-nido-carborane conjugates as boron delivery agents to tumour cells for application in BNCT.
Subject(s)
Boron , Glioblastoma , Humans , Boron/pharmacology , Amides , Folic Acid/pharmacology , ThinnessABSTRACT
A new group of nido-carboranyl derivatives of natural (S)-amino acids containing from 9 to 18 boron atoms was obtained in good yields as a result of acylation of 3-amino-1,2-dicarba-closo-dodecaborane followed by deboronation. The proposed approach is convenient and based on the use of readily available reagents and is suitable for the synthesis of enantiopure nido-carboranyl derivatives of amino acids with various side chains, including water-soluble boron-containing amino acids (17 examples).