Synthesis and cytotoxicity of the boron carrier pentagamaboronon-0-ol for boron neutron capture therapy against breast cancer

Rohmad Yudi Utomo; Febri Wulandari; Dhania Novitasari; Ratna Asmah Susidarti; Mitsunori Kirihata; Adam Hermawan; Edy Meiyanto

doi:10.4103/japtr.japtr_220_21

Synthesis and cytotoxicity of the boron carrier pentagamaboronon-0-ol for boron neutron capture therapy against breast cancer

J Adv Pharm Technol Res. 2022 Jan-Mar;13(1):70-76. doi: 10.4103/japtr.japtr_220_21. Epub 2022 Jan 21.

Authors

Rohmad Yudi Utomo^{1

2}, Febri Wulandari¹, Dhania Novitasari¹, Ratna Asmah Susidarti^{1

3}, Mitsunori Kirihata³, Adam Hermawan^{1

4}, Edy Meiyanto^{1

4}

Affiliations

¹ Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada Sekip Utara II, Yogyakarta, Indonesia.
² Department of Pharmaceutical Chemistry, Laboratory of Medicinal Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada Sekip Utara II, Yogyakarta, Indonesia.
³ Research Center of Boron Neutron Capture Therapy, Research Organization for the 21 Century, Osaka Prefecture University, Osaka, Japan.
⁴ Department of Pharmaceutical Chemistry, Laboratory of Macromolecular Engineering, Faculty of Pharmacy, Universitas Gadjah Mada Sekip Utara II, Yogyakarta, Indonesia.

Abstract

Boronic acid-containing curcumin analog, pentagamaboronon-0 (PGB-0), acts as a potential boron-carrier agent but has limited water solubility. Thus, a new compound (PGB-0-ol) with better chemical and pharmacological properties than PGB-0 has been synthesized. Molecular docking was performed using a molecular operating environment. Prediction of PGB-0-ol absorption, distribution, metabolism, and excretion (ADME) was performed using pkCSM software. PGB-0-ol was synthesized by adding NaBH₄ to PGB-0 and stirring for 1 h. The crude PGB-0-ol was purified using preparative layer chromatography. Cell viability was evaluated using the trypan blue exclusion assay. In comparison to PGB-0 based on molecular docking study, PGB-0-ol could interact in with several cancer biomarkers, such as human epidermal growth factor2 epidermal growth factor receptor, IκB kinase, folate receptor-α, and integrin α_vβ₃. PGB-0-ol also showed an improved ADME profile because of its higher water solubility than PGB-0. PGB-0-ol was synthesized by selective ketone reduction of PGB-0 into primary alcohol by sodium borohydrate producing 30% yield. The cytotoxicity of PGB-0-ol against several breast cancer cells was lower than that of PGB-0. The novel compound PGB-0-ol was synthesized using simple steps. PGB-0-ol has low cytotoxicity against breast cancer cells and could be applied in boron neutron capture therapy as a boron carrier.

Keywords: Boron carrier; cytotoxicity; molecular docking; pentagamaboronon-0-ol; synthesis.