Synthesis And Application Of Molecular Probes Of Sinomenine Derivatives

Sinomenine,an alkaloid isolated from the Chinese medicinal plant Sinomenium acutum,exhibits a variety of pharmacological activities including anti-inflammatory,immunosuppressive,analgesic,antihypertensive and antiarrhythmic effects.Due to weak activity of sinomenine monomer,large doses are often used,and its mechanism of action in vivo remains unclear.Several new types of sinomenine derivatives have been studied in our group,in which the pyrazine derivative 1020 and derivative YL064 significantly inhibited the inflammatory factors.In this paper,in order to explore the mechanism and biological target of sinomenine,synthesis of molecular probes of sinomenine derivative YL064 was studied.The design and synthesis of a series of crucial label were accomplished,including photoaffinity labeled probe compound 108,biotin-labeled probe compound 123 and compound 124,fluorescently labeled probe compound 143 and a biotin-labeled inactive compound 149.In addition,a biotin-labeled compound 158 was also used as negative control.The test and comparison of physiological activity against multiple myeloma(MM)cells,revealed that biotin-labeled compound 124 exhibits significant induction of apoptosis of MM cells.Data of compound 149 verified that the C10 aryl mercapto group position of the sinomenine derivatives might be a key group to the apoptosis of MM cells.The activity comparison of compound 158 and 124 interprets that whether the conjugate C=C bond plays a role in the protein capture.