Eleven isoquinoline alkaloids on inhibiting tissue factor activity: structure-activity relationships and molecular docking.

Abstract

Tissue factor (TF) which plays a key role in hemostasis and thrombosis appears to be an attractive target and medicinal plants having alkaloids inhibition TF activity benefit to cardiovascular disease (CVD). The aim of study is to explore further knowledge about alkaloids and TF. TF procoagulant activities were determined by the simplified chromogenic assay and their mRNA expression were then examined by reverse transcription and polymerase chain reaction. Besides, the potential of TF/FVIIa binding with four representative alkaloids were analyzed by molecular docking. The results indicated that these isoquinoline alkaloids with various structures had a different effect on suppression of TF activity. Molecular docking showed four alkaloids including l-corydalmine, berberine, jatrorrhizine, and tetrahydropalmatine were stably posed in the active binding pocket of TF/FVIIa. The SARs analysis showed the structural difference including planar, quaternary nitrogen, and the peripheral functional groups at C-8, C-9, C-10, have strong effect on inhibition of TF activity, which provided effective methods to modify isoquinoline alkaloids for inhibiting TF activity. This study provides a further evidence for the cardiovascular protection of isoquinoline alkaloids, and has physiological significance in the clinical challenge to use isoquinoline alkaloids or their potential analogs in the treatment of CVD.