报告题目：Development of Organic Carbon Monoxide Prodrugs
报 告 人：潘志祥（佐治亚州立大学）
Zhixiang Pan held his PhD in Organic Chemistry from Georgia State University in May 2019. His Ph.D. work focuses on the development of a series of organic Carbon Monoxide (CO) prodrugs as prototypes of “carbon monoxide in a pill.” He has developed a series of CO prodrugs with tunable CO release kinetics. In addition, he has designed several CO prodrugs with different triggered release mechanisms for targeted delivery. The results of his past work have been published in J. Med. Chem, Org. Lett, Chem. Eur. J and Eur. J. Med. Chem.
CO is an endogenously produced gasotransmitter in mammals and may have signalling roles in bacteria as well. It has many recognized therapeutic effects. A significant challenge in this field is the development of pharmaceutically acceptable forms of CO delivery with controllable and tunable release rates. In the past five years, a series of such CO prodrugs was synthesized to examine the structure-release rate in aqueous solution at neutral pH.
Also, we focused on the development of reactive oxygen species ROS-sensitive CO prodrugs, which selectively deliver CO to cells with elevated ROS levels and sensitize cancer cells to chemotherapy. CO prodrugs as such could serve as powerful tools for targeted delivery to disease sites with elevated ROS levels and for exploring the therapeutic applications of CO.
In addition, we focused on the development of metal-free CO prodrugs with dual-responsive endogenous triggers, which have the advantage of controlled activation at the desired site of action. These CO prodrugs afford highly selective release profiles as compared to others with no or a single trigger.One representative CO prodrug in this category showed significant anti-inflammatory effects both in vitro and in vivo.