Azanonaboranes Containing Imidazole Derivatives for Boron Neutron Capture Therapy: Synthesis, Characterization, and In Vitro Toxicity Evaluation

Abstract

A number of azanonaboranes containing imidazole derivatives have been synthesized by a ligand-exchange reaction. The exo-NH(2)R group of the azanonaborane of the type [(RH(2)N)B(8)H(11)NHR] can be exchanged by one hetero-nitrogen atom of the imidazole ring. In the case of histamine, the exchange takes place on the aliphatic amino group, the hetero-nitrogen atom of the imidazole ring or both of them. The products were confirmed by NMR, IR spectroscopy, elemental analysis, and mass spectrometry. The electron-withdrawing effect of the nitro group in 2-nitroimidazole is the main hindrance to achieve the exchange reaction. In vitro experiments were performed with B16 melanoma cells. A comparison of the biological properties of the products in which the B(8)N cluster is connected to the hetero-nitrogen atom of imidazole ring or the aliphatic NH(2) group showed that incorporation of B(8)N cluster unit into primary amino group increases the compound's toxicity. In contrast, this specificity for cytotoxicity effect was not observed in the case of histamine containing two B(8)N clusters which was relatively nontoxic and did not inhibit colony formation up to concentrations of 2 mM.

Synthesis and characterization of azanonaborane-containing purine derivatives for boron neutron capture therapy

“…The exo amine ligand (RNH 2 ) can be readily replaced with other primary or secondary amines [29]. Aliphatic amines can be replaced with pyridine [30,31] or imidazole [26] derivatives. In line with these results, we found it is possible to exchange the RNH 2 group with purine or purine derivatives to synthesize new azanonaborane clusters containing a purine moiety.…”

“…For some years, we have been working on the synthesis and structural and biological evaluation of azanonaborane by incorporating polar functional groups [19][20][21][22], porphyrins [23,24], sugars [25], or heterocyclic bases [26] with the hope of achieving properties suitable for BNCT: high and differential accumulation of boron, by using compounds with low toxicity, high boron content, and moieties suitable for physiological targeting. The in vitro cytotoxicity of various functionalized azanonaborane clusters was reported [19][20][21][22][23][24][25][26]. The cluster itself appears not to have a high toxic potential [19][20][21][22][23][24][25][26].…”

“…The in vitro cytotoxicity of various functionalized azanonaborane clusters was reported [19][20][21][22][23][24][25][26]. The cluster itself appears not to have a high toxic potential [19][20][21][22][23][24][25][26]. Among a large number of molecules examined, the B 8 N containing sugars [25] displayed good cell survival over a wide range of boron concentrations even at higher boron concentration (300 µg boron mL -1 , corresponding to a compound concentration of 3.5 mM).…”

Synthesis, characterization, and spectrophotometric studies of novel fluorescent arachno decaborane and nonaborane clusters containing aza-distyrylbenzene derivatives

“…The alcoholysis of bis (dimethyl sulfide)-arachno-decaborane using methanol led to the formation of dimethyl sulfide-arachno-nonaborane {4-Me 2 SB 9 H 13 } [7]. Both of these borane clusters undergo several interesting reactions [8][9][10][11][12][13][14][15]. The open-faced arachno 10 or nine-vertex borane residues will permit tailoring of the borane residues, for example by the addition of metal centers as exemplified by the reaction between {Co 2 (CO) 8 } and the monomer precursor unit {6,9-(Et 2 S) 2 B 10 H 12 } to give {(CO) 6 CoB 10 H 8 (Et 2 S) 2 } [16].…”

“…The bis (dimethyl sulfide) adduct of decaborane (14) {6,9-(Me 2 S) 2 B 10 H 12 } is one of several compounds that is easily prepared by reacting decaborane (B 10 H 14 ) and a Lewis base [4][5][6]. The alcoholysis of bis (dimethyl sulfide)-arachno-decaborane using methanol led to the formation of dimethyl sulfide-arachno-nonaborane {4-Me 2 SB 9 H 13 } [7].…”