Research Of The New Drug That Disrupt Psd95/nNOS Interaction

Ischemic stroke remains a leading cause of death and disability worldwide. Numerous studies have shown that excessive amounts of NO which can mediate tissue injury are generated according to the following NMDA receptor /PSD95/nNOS pathway. PSD-95 mediates the coupling of nNOS to NMDA receptors in the central nervous system.Baicalin can disrupt PSD-95/nNOS pathway and reduce the releasing of NO. More particularly, the compound is directed to disrupting agents that dislocate nNOS from PSD-95 and related proteins, and thereby interfere with the NMDA receptor/PSD-95/nNOS pathway. The agents need not affect the catalytic activity of nNOS or the catalytic activity of other NOS isoforms.According to leading compound Baicalin, I have designed and synthesized three kinds of 26 novel compounds which may be used as neuroprotection agents that disrupt PSD-95/nNOS interaction. The structures have been confirmed by 1HNMR and MS.The bioassays of some compounds have been done. The results of activity test suggest that some of them have strong activity which can disrupt PSD-95/nNOS pathway.