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Synthesis and cytotoxicity of the boron carrier pentagamaboronon-0-ol for boron neutron capture therapy against breast cancer
Rohmad Yudi Utomo1, Febri Wulandari2, Dhania Novitasari2, Ratna Asmah Susidarti1, Mitsunori Kirihata3, Adam Hermawan4, Edy Meiyanto4
1 Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada Sekip Utara II; Department of Pharmaceutical Chemistry, Laboratory of Medicinal Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada Sekip Utara II, Yogyakarta, Indonesia
2 Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada Sekip Utara II, Yogyakarta, Indonesia
3 Research Center of Boron Neutron Capture Therapy, Research Organization for the 21st Century, Osaka Prefecture University, Osaka, Japan
4 Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada Sekip Utara II; Department of Pharmaceutical Chemistry, Laboratory of Macromolecular Engineering, Faculty of Pharmacy, Universitas Gadjah Mada Sekip Utara II, Yogyakarta, Indonesia
Correspondence Address:
Prof. Edy Meiyanto
Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada Sekip Utara II, Yogyakarta 55281; Department of Pharmaceutical Chemistry, Laboratory of Macromolecular Engineering, Faculty of Pharmacy, Universitas Gadjah Mada Sekip Utara II, Yogyakarta 55281
Indonesia
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/japtr.japtr_220_21
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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 αvβ3. 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.
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