Synthesis and Cytotoxic Activity of 2,5-Bis(4-Boronic Acid)benzylidine Cyclopentanone on Her2 Overexpressed-Cancer Cells

Abstract

Development of chemotherapeutic agent and boron carrying pharmaceutical based on HER2 specific targeted is important due to its role in enhancing cancer progression. The purpose of this study is to synthesize curcumin analogue, namely Pentagamaboron-0 (PGB-0) or 2,5-bis(4-boronic acid)benzylidine cyclopentanone, and to explore the cytotoxic activity on HER2 overexpressed-cancer cells. MCF-7/HER2 was used as a model of HER2 overexpressed-cancer cells and NIH3T3 as normal cells. PGB-0 bound to ATP binding site of HER2 and EGFR based on molecular docking study. PGB-0 was synthesized resulting in 33% yield and was confirmed by IR, 1 HNMR, 13 CNMR and Mass spectroscopy. Based on MTT assay PGB-0 decreased cells viability on MCF-7/HER2 cells with IC 50 value of 270µM but performed no effect on NIH3T3 cells. Cell cycle analysis revealed that PGB-0 increased sub-G1 accumulation. PGB-0 decreased HER2 expression in a dose-dependent manner. We conclude that the new compound PGB-0 inhibits cell growth through cell death induction and decreased HER2 expression. Thus, PGB-0 is potential to be developed as a chemotherapeutic agent and boron carrying pharmaceutical targeted on the HER2 receptor.

Anti-metastatic effect of curcumin analog pentagamaboronon-0-fructose (PGB-0-F) against 4T1 breast cancer cells

“…Previous study showed that PGB-0-F as an anti-cancer agent which has cytotoxic effect of 4T1 cells with IC 50 values of 33 µM (Meiyanto et al, unpublished data), while PGB-0 has IC 50 value of 300 µM in 4T1 cells (Kusumastuti et al, unpublished data), and 270 µM in MCF-7/Her2 cells (Utomo et al 2017). In this present study, we also observed the inhibition of cancer cell migration as the one of parts of metastasis process by treatment of PGB-0-F through scratch wound healing assay.…”

“…In addition, K-PGV-0, a soluble form of PGV-0 also performed anti-migratory effect on highly metastasis breast cancer (Putri et al 2016). Dibenzilidine boronic acid cyclopentanone (DBBAC) or pentagamaboronon-0 (PGB-0) is a novel boron containing-curcumin analog which is designed and synthesized by Cancer Chemoprevention Research Center, Universitas Gadjah Mada based on the benzylidine cyclopentanone structure (Utomo et al 2017). This compound has been explored for the anticancer activity and boron carrying pharmaceutical for BNCT (Boron Neuton Capture Therapy).…”

“…This compound has been explored for the anticancer activity and boron carrying pharmaceutical for BNCT (Boron Neuton Capture Therapy). PGB-0 pos-sessed cytotoxic effect on MCF-7/HER2 cells through decreasing HER2 expression (Utomo et al 2017). On the other hand, PGB-0 also performed anti-migratory effect against 4T1 breast cancer cells by modulating cell cycle, inducing apoptosis, inhibiting migration, and decreasing MMP-9 expression (soon will be publised).…”

Pentagamaboronon-0 Fructose Inhibited Migration and Overexpression of Matrix Metalloproteinases 9 on MCF-7/HER2 Breast Cancer Cells

“…Recent study reveals that PGB-0 have cytotoxic activity on MCF-7/ HER2 breast cancer cells by modulated cell cycle in G1 phase. This activity is thought to be caused by binding of PGB-0 in the tyrosine kinase part of HER2 as evidenced by a decrease in HER2 expression in PGB-0 treatment (Utomo, et al, 2017). PGB-0 in combination with doxorubicin also showed antimigration by decreased the MMP-9 expression on 4T1 cells (CCRC unpublised data).…”

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

“…The low cytotoxic effect (IC 50 > 200 μM) on HER2-expressed breast cancer cells, no toxic effect against normal fibroblast cells, and comparable with lapatinib and curcumin on the interaction with HER2 are the current modality of PGB-0 as novel boron carrier (5).…”