5-(Bis(3-(2-hydroxyethyl)-1H-indol-2-yl)methyl)-2-hydroxybenzoic acid(BHIMHA):showing a strategy of

• 作 者: Taiping Gan Yuji Wang Ming Zhao Jianhui Wu Jian Yang Shiqi Peng
• 机 构: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs,Engineering Research Center of En
• 出 处: 2016年北京药学年会
• 发表日期: 2016年8期
• 关键词: migration invasion lung metastasis anticancer anti-inflammation PKCα inhibitor

　　Early metastasis is still the most recalcitrant factor in the treatment of lung cancer patients.By analyzing the structures and comparing the docking scores of the known pharmacophores,the authors of this paper designed 5-(bis(3-(2-hydroxyethyl)-1H-indol-2-yl)methyl)-2-hydroxybenzoic acid(BHIMHA)as a promising lead compound to develop metastasis inhibitors.In vitro 5,10,and 20 μM of BHIMHA concentration dependently inhibited the migration and invasion of A549 cells.In vivo 0.4,2.0,and 8.9 μmol/kg of BHIMHA dose dependently inhibited the metastasis of LLC(Lewis Lung Carcinoma)toward lung.In vivo,2 μmol/kg of BHIMHA showed additional actions of slowing the growth of the primary tumor of C57BL/6 mice and S180 mice as well as inhibiting xylene-induced ear edema of the mice.Therefore,BHIMHA simultaneously blocked tumor metastasis toward lung,slowed the primary tumor growth,and limited the inflammation.These pharmacological actions were correlated with the inhibition of PKCα and NF-κB expression.