Anthraquinones from Cassiae semen as thrombin inhibitors: in vitro and in silico studies

Publication date: September 2019Source: Phytochemistry, Volume 165Author(s): Xiao Yu, Ling-Hua Wei, Jia-Kai Zhang, Tian-Ran Chen, Qiang Jin, Yi-Nan Wang, Shui-Jun Zhang, Tong-Yi Dou, Yun-Feng Cao, Wen-Zhi Guo, Guang-Bo Ge, Ling YangAbstractThrombin inhibitor therapy is one of the most effective therapeutic strategies for the prevention and treatment of cardiovascular and thrombotic diseases. Although several marketed direct thrombin inhibitors (DTIs) have been widely used in clinic, the potentially serious complications of these DTIs prompted the researchers to find more DTIs with improved safety profiles. Herein, we report that natural anthraquinones in Cassiae semen (the seed of Cassia obtusifolia L. or C. tora L.), including obtusifolin, obtusin, aurantio-obtusin and chryso-obtusin, display strong to moderate inhibition on human thrombin, with the IC50 values ranging from 9.08 μM to 27.88 μM. Further investigation on the inhibition kinetics demonstrates that these anthraquinones are mixed inhibitors against thrombin-mediated Z-GGRAMC acetate hydrolysis, while obtusifolin and aurantio-obtusin show strong thrombin inhibition capacity, with the Ki values of 9.63 μM and 10.30 μM, respectively. Docking simulations demonstrate that both obtusifolin and aurantio-obtusin can simultaneously bind on the catalytic cavity and the two anion binding exosites (ABE1 and ABE2), while the hydroxyl group at the C-7 site and the methoxyl group at the C-8 site can create key inter...
Source: Phytochemistry - Category: Chemistry Source Type: research