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, 1HNMR, 13CNMR and Mass spectroscopy. Based on MTT assay PGB-0
decreased cells viability on MCF-7/HER2 cells with IC50 value of 270 µM 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.
Keywords: Synthesis of PGB-0;
MCF7/HER-2; cytotoxic
Author: Rohmad Yudi Utomo,
Herwandhani Putri, Pudjono, Ratna Asmah Susidarti, Riris Istighfari Jenie, Edy
Meiyanto
Journal Code: jpfarmasigg170017
