Preparation of pentagamaboronon-0 and its fructose and sorbitol complexes as boron carrier for boron neutron capture therapy (BNCT) applicatio

Ratna Asmah Susidarti , Rohmad Yudi Utomo, Lailatul Qodria, Ratna Dwi Ramadani, Youichiro Ohta, Yoshihide Hattori, Mitsunori Kirihata, Edy Meiyanto

Abstract


Development of specific and selective boron carriers is indispensable for boron neutron capture therapy (BNCT) application. Pentagamaboronon-0 (PGB-0) is a promising candidate as boron carrier compound  due to the low but selective cytotoxicity in breast cancer cells. Formerly we reported synthesis of PGB-0 which was ineffective due to its low aqueous solubility. In the present study, we, therefore, introduced  the new PGB-0 preparation complexed with sugars to increase its solubility in water. By synthesizing  at room temperature and using flash chromatography for the purification, we produced PGB-0 with a yield of 40%. PGB-0 fructose complex (PGB-0-F) and PGB-0 sorbitol complex (PGB-0-Sor)  were obtained with smaller particle size compared to PGB-0 suspension in water. Based on the MTT assay, the cytotoxicity of PGB-0-F and PGB-0-Sor were higher than PGB-0 even though still categorized  as low cytotoxic agents. In conclusion, we provided PGB-0 with a new method and improved its solubility in water. Further investigations are still needed to develop more efficient PGB-0 as boron carrier  for BNCT in various cancers.


Keywords


BNCT; Boron carrier; Fructose and sorbitol complexes; PGB-0.

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Barth RF, Zhang Z, Liu T. A realistic appraisal of boron neutron capture therapy as a cancer treatment modality. Cancer Commun (Lond). 2018;38(1): 36-42.

Takahara K, Inamoto T, Minami K, Yoshikawa Y, Takai T, Ibuki N, et al. The anti-proliferative effect of boron neutron capture therapy in a prostate cancer xenograft model. PLoS One. 2015;10(9):e0136981.

Bendel P, Margalit R, Salomon Y. Optimized1H MRS and MRSI methods for the in vivo detection of boronophenylalanine. Magn Reson Med. 2005;53(5):1166-1171.

Watanabe T, Hattori Y, Ohta Y, Ishimura M, Nakagawa Y, Sanada Y, et al. Comparison of the pharmacokinetics between L-BPA and L-FBPA using the same administration dose and protocol: a validation study for the theranostic approach using [18F]-L-FBPA positron emission tomography in boron neutron capture therapy. BMC Cancer. 2016;16(1):859-868.

Utomo RY, Putri H, Pudjono P, Susidarti RA, Jenie RI, Meiyanto E. Synthesis and cytotoxic activity of 2,5-bis(4-boronic acid)benzylidine cyclopentanone on HER2 overexpressed-cancer cells. Indones J Pharm. 2017;28(2):74-81.

Cunico LP, Acosta MC, Turner C. Experimental measurements and modeling of curcumin solubility in CO2-expanded ethanol. J Supercrit Fluids. 2017;130:381-388.

Xu DH, Wang S, Mei XT, Luo XJ, Xu SB. [Studies on solubility enhancement of curcumin by Polyvinylpyrrolidione K30]. Zhong Yao Cai. 2008;31(3):438-442.

Istyastono EP, Siwi SU, Utama AA, Supardjan AM. Synthesis new potential anti-inflammatory agent sodium salt of pentagamavunon-0. Indones J Chem. 2004;4(3):180-185.

Margono SA, Verawati EY. Synthesis of potassium pentagamavunonat-0 using potassium hydroxyde and solvent tertrahydrofuranethanol. Indonesian J Pharm. 2005;16:239-245.

Feng T, Wei Y, Lee RJ, Zhao L. Liposomal curcumin and its application in cancer. Int J Nanomedicine. 2017;12:6027-6044.

Emami J, Mohiti H, Hamishehkar H, Varshosaz J. Formulation and optimization of solid lipid nanoparticle formulation for pulmonary delivery of budesonide using Taguchi and Box-Behnken design. Res Pharm Sci. 2014;10(1):17-33.

Barth RF, Vicente MGH, Harling OK, Kiger WS, Riley KJ, Binns PJ, et al. Current status of boron neutron capture therapy of high grade gliomas and recurrent head and neck cancer. Radiat Oncol. 2012;7(1):146-166.

Shull BK, Spielvogel DE, Head G, Gopalaswamy R, Sankar S, Devito K. Studies on the structure of the complex of the boron neutron capture therapy drug, L‐p‐boronophenylalanine, with fructose and related carbohydrates: chemical and 13C NMR evidence for the beta‐D‐fructofuranose 2,3,6‐(p‐phenylalanylorthoboronate) structure. J Pharm Sci. 2000;89(2):215-222.

Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65(1):55-63.

Yinghuai Z, Cheng Yan K, Maguire JA, Hosmane NS. Recent developments in boron neutron capture therapy driven by nanotechnology. Curr Chem Biol. 2007;1(2):147-163.

Roos Y, Karel M. Plasticizing effect of water on thermal behavior and crystallization of amorphous food models. J Food Sci. 1991;56(1):38-43.

Hattori Y, Kurihara K, Kondoh H, Asano T, Kirihata M, Yamaguchi Y, et al. Biological evaluation of fluorinated p-boronophenylalanine derivatives as a boron carrier. Protein Pept Lett. 2007;14(3): 269-272.

Sebaugh JL. Guidelines for accurate EC50/IC50 estimation. Pharm Stat. 2011;10(2):128-134.

Kirihara M, Morimoto T, Ichimoto I. A Simple and improved synthesis of p-boronophenylalanine, a boron carrier for the boron-neutron capture therapy. Biosci Biotechnol Biochem. 1993;57(11):1940-1941.

Harada S, Kajihara R, Muramoto R, Jutabha P, Anzai N, Nemoto T. Catalytic asymmetric synthesis of α-methyl-p-boronophenylalanine. Bioorg Med Chem Lett. 2018;28(10):1915-1918.

Soloway AH, Tjarks W, Barnum BA, Rong FG, Barth RF, Codogni IM, et al. The chemistry of neutron capture therapy. Chem Rev. 1998;98(4):1515-1562.

Iravani S, Korbekandi H, Mirmohammadi SV, Zolfaghari B. Synthesis of silver nanoparticles: chemical, physical and biological methods. Res Pharm Sci. 2014;9(6):385-406.

Mousavi S, Forootanfar H, Faramarzi M, Ameri A, Shakibaie M. Metal nanoparticle production assisted by α-amylase. Res Pharm Sci. 2012;7(5):S218.

Chen BG, Zhang MY, Zhao YY, Zhang J, Sun CC. Structural and electronic properties of BPA-fructose complex used in boron neutron capture therapy. J Mol Struct THEOCHEM. 2006;766(1):35-40.

English DP, Roque DM, Santin AD. HER2 expression beyond breast cancer: therapeutic implications for gynecologic malignancies. Mol Diagn Ther. 2013;17(2):85-99.

Mitri Z, Constantine T, O’Regan R. The HER2 receptor in breast cancer: pathophysiology, clinical use, and new advances in therapy. Chemother Res Pract. 2012;2012. Article ID 743193. DOI: 10.1155/2012/743193.

Gupta S. Triple negative breast cancer: A continuing challenge. Indian J Med Paediatr Oncol. 2013;34(1):1-2.

Bianchini G, Balko JM, Mayer IA, Sanders ME, Gianni L. Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease. Nat Rev Clin Oncol. 2016;13(11):674-690.

Hattori Y, Kusaka S, Mukumoto M, Uehara K, Asano T, Suzuki M, et al. Biological evaluation of dodecaborate-containing L-amino acids for boron neutron capture therapy. J Med Chem. 2012;55(15):6980-6984.

Miyahara T, Ueda K, Akaboshi M, Shimada Y, Imamura M, Utsumi H. Hyperthermic enhancement of cytotoxicity and increased uptake of cis‐diamminedichloroplatinum(ii) in cultured human esophageal cancer cells. Jpn J Cancer Res. 1993;84(3):336-340.


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