Tanshinone-IIA-Based Analogues of Imidazole Alkaloid Act as Potent Inhibitors To Block Breast Cancer Invasion and Metastasis in Vivo

  • J Med Chem. 2018 Dec 13;61(23):10488-10501. doi: 10.1021/acs.jmedchem.8b01018.
Qiong Wu  1 ,  Kangdi Zheng  1 ,  Xiaoting Huang  1 ,  Li Li  1 ,  Wenjie Mei  1  2  3
Affiliations
  • 1. School of Pharmacy , Guangdong Pharmaceutical University , Gaungzhou , 510006 , China.
  • 2. Guangdong Province Engineering Technology Centre for molecular Probe & Bio-medicine Imaging , Guangdong Pharmaceutical University , Guangzhou 510006 , China.
  • 3. Guangzhou key laboratory of construction and application of new drug screening model systems , Guangdong Pharmaceutical University , Guangzhou 510006 , China.
PMID: 30398868 DOI: 10.1021/acs.jmedchem.8b01018
Abstract

Tanshinone-IIA (Tan-IIA), a primary active component extracted from commonly used Chinese herbal, Salvia miltiorrhiza (Danshen), is considered as a potential inhibitor against tumor cell proliferation. However, the potential application of Tan-IIA is hindered by its poor water solubility and low bioavailability. In this work, an imidazole moiety was linked to the skeleton of Tan-IIA to enhance its antitumor activity. A series of Tan-IIA-based analogues TA01-TA12 were synthesized, and their inhibitory activities against the migration and invasion of MDA-MB-231 cells were investigated. All compounds, particularly TA12, markedly inhibited the proliferation, migration, and invasion of MDA-MB-231cells. TA12 also prominently blocked Cancer cell metastasis in blood vessels and surrounding tissues in zebrafish xenograft model. Further studies showed that the mechanisms may involve S-phase arrest pathway, which was probably caused by inducing Reactive Oxygen Species production and activating DNA damage. These results indicated that the Tan-IIA-based analogues of imidazole derivates can act as potent antimetastasis agents.