20(S)-Protopanaxadiol (PPD) analogues chemosensitize multidrug-resistant cancer cells to clinical anticancer drugs |
| |
| Authors: | Junhua Liu Xu Wang Peng Liu Rongxin Deng Min Lei Wantao Chen Lihong Hu |
| |
| Institution: | 1. Shanghai Research Center for Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China;2. Department of Oral and Maxillofacial—Head and Neck Oncology, Ninth People’s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200011, PR China |
| |
| Abstract: | Novel 20(S)-protopanoxadiol (PPD) analogues were designed, synthesized, and evaluated for the chemosensitizing activity against a multidrug resistant (MDR) cell line (KBvcr) overexpressing P-glycoprotein (P-gp). Structure–activity relationship analysis showed that aromatic substituted aliphatic amine at the 24-positions (groups V) effectively and significantly sensitized P-gp overexpressing multidrug resistant (MDR) cells to anticancer drugs, such as docetaxel (DOC), vincristine (VCR), and adriamycin (ADM). PPD derivatives 12 and 18 showed 1.3–2.6 times more effective reversal ability than verapamil (VER) for DOC and VCR. Importantly, no cytotoxicity was observed by the active PPD analogues (5 μM) against both non-MDR and MDR cells, suggesting that PPD analogues serve as novel lead compounds toward a potent and safe resistance modulator. Moreover, a preliminary mechanism study demonstrated that the chemosensitizing activity of PPD analogues results from inhibition of P-glycoprotein (P-gp) overexpressed in MDR cancer cells. |
| |
| Keywords: | Multidrug resistant P-glycoprotein Chemosensitizer Structure–activity relationship |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
