@article{APS10158,
author = {Yi Liu and Ke-xin Zhu and Lei Cao and Zhi-fu Xie and Min Gu and Wei Lü and Jing-ya Li and Fa-jun Nan},
title = {Berberine derivatives with a long alkyl chain branched by hydroxyl group and methoxycarbonyl group at 9-position show improved anti-proliferation activity and membrane permeability in A549 cells},
journal = {Acta Pharmacologica Sinica},
volume = {41},
number = {6},
year = {2020},
keywords = {},
abstract = {Berberine (BBR) exhibits diverse bioactivities, including anticancer activity; but its poor druggability limits its applications. In this study, we designed and synthesized a series of 9-O position modified BBR derivatives aiming to improve its cell permeability and anticancer activity, utilizing a long alkyl chain branched by hydroxyl group and methoxycarbonyl group. Among these compounds, B10 showed 3.6-fold higher intracellular concentration than BBR, as well as 60-fold increased anti-proliferation activity against human lung cancer A549 cells compared with BBR. Treatment with B10 (1, 2 μM) induced apoptosis of A549 cells. Further investigations showed that B10 treatment dose-dependently affected mitochondrial functions, including oxygen consumption rate (OCR), mitochondrial membrane potential (MMP) and the morphology of mitochondria in A549 cells. Therefore, this work offers a new way for BBR structural modification through improving cell membrane permeability to affect mitochondrial functions and potential anti-tumor therapy in the future.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/10158}
}