Synthesis of 3'- O-alkyl homologues and a biotin probe of isorhamnetin and evaluation of cytotoxic efficacy on cancer cells

Chem Biodivers. 2021 Sep 24. doi: 10.1002/cbdv.202100301. Online ahead of print.ABSTRACTIsorhamnetin is a natural flavonoid which shows a variety of biological activities such as antioxidant, anti-inflammation and antitumor. In order to identify the cellular binding protein of isorhamnetin as potential anti-cancer target, we first synthesized 3'- O -substituted quercetin as isorhamnetin analogues and evaluated the growth inhibitory activity of these derivatives on breast, colon and prostate cancer cell lines. The preliminary results showed that the 3'- O modification did not affect the cytotoxic activity of the scaffold. Analysis of the co-crystal structure and the docking pose of isorhamnetin with reported binding protein of isorhamnetin or quercetin indicated the 3'- O -substitution groups located outside of the binding pocket, which is in accordance with activity of 3'- O derivatives. Then a biotin conjugate of isorhamnetin with a tetraethylene glycol (PEG) 4 linker at the 3' position was synthesized and the resulting probe retained the anti-proliferative activity on cancer cell lines, the cellular fluorescence analysis showed the distribution of probe inside the cells which indicated the probe had limited cell permeability. Finally, pull down assay both in situ inside cells and in the cell lysates indicated the isorhamnetin biotin probe was capable of protein labeling in cell lysates. These findings provide the isorhamnetin 3'- O -biotin probe as a tool to reveal the targ...
Source: Chemistry and Biodiversity - Category: Biochemistry Authors: Source Type: research