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Synthesis and in vitro evaluation of thiododecaborated α, α- cycloalkylamino acids for the treatment of malignant brain tumors by boron neutron capture therapy

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Abstract

Boron-neutron capture therapy (BNCT) is an attractive technique for cancer treatment. As such, α, α-cycloalkyl amino acids containing thiododecaborate ([B12H11]2−-S-) units were designed and synthesized as novel boron delivery agents for BNCT. In the present study, new thiododecaborate α, α-cycloalkyl amino acids were synthesized, and biological evaluation of the boron compounds as boron carrier for BNCT was carried out.

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Abbreviations

BNCT:

Boron neutron capture therapy

L-10BPA:

p-(10B)borono-l-phenylalanine

10BSH:

Mercapto-undeca-hydro-closo-dodeca(10B)borate

ACBC:

1-Aminocyclo-butane-1-carboxylic acid

PET:

Positron emission tomography

ICP-OES:

Inductively coupled plasma optical emission spectrometry

LAT:

L-type amino acid transporter

EAATs:

Excitatory amino acid transporters

ODS:

Octadecylsilyl

WST:

Water soluble tetrazolium

DMEM:

Dulbecco’s Modified Eagle’s Medium

FBS:

Fetal bovine serum

EDTA:

Ethylenediaminetetraacetic acid

HEPES:

4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid

PBS:

Phosphate-buffered saline

NMR:

Nuclear magnetic resonance

ESI–MS:

Electrospray ionization mass spectrometry

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Acknowledgments

This work was supported by the Adaptable and Seamless Technology Transfer Program through target-driven R&D, JST. We thank Professor K. Ogawa of Osaka Prefecture University for his technical support with immunostaining. We also thank Mr. H. Nakashima and Ms. Y. Ishino for the measurement of the ESI-MS.

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The authors have declared no conflict of interest.

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Correspondence to Yoshihide Hattori.

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Hattori, Y., Kusaka, S., Mukumoto, M. et al. Synthesis and in vitro evaluation of thiododecaborated α, α- cycloalkylamino acids for the treatment of malignant brain tumors by boron neutron capture therapy. Amino Acids 46, 2715–2720 (2014). https://doi.org/10.1007/s00726-014-1829-5

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