Plinabulin,a potent microtubule-targeting agent,is derived from marine natural diketopiperazine ‘phenylahistin'.To develop novel plinabulin analogue that could display better pharmacokinetic properties and less s...Plinabulin,a potent microtubule-targeting agent,is derived from marine natural diketopiperazine ‘phenylahistin'.To develop novel plinabulin analogue that could display better pharmacokinetic properties and less side effects,deuterated plinabulin 9 was synthesized and evaluated in vitro and in vivo.In comparison with plinabulin,in vivo pharmacokinetic studies indicated that the deuterated derivative 9 could alter blood circulation behavior obviously,which was proved by increased area under the plasma concentration-time curve(AUC_(0–∞)),reduced clearance(CL),and prolonged total body mean residence time(MRT).The derivative 9 also has higher inhibition rates against Bx PC-3,Jurkat and A-431 tumor cell lines as compared with its prototype plinabulin.Therefore,the deuterated compound 9 might be developed as a potential agent for different cancer treatments.展开更多
基金supported by‘Zhufeng Scholar Program’of Ocean University of China(No.841412016)‘Major Projects of Independent Innovation’of Qingdao(15-4-13-zdzx-hy)‘Outstanding Talents Plan’of Qingdao(15-10-3-15-(34)-zch)to Dr.Wenbao Li
文摘Plinabulin,a potent microtubule-targeting agent,is derived from marine natural diketopiperazine ‘phenylahistin'.To develop novel plinabulin analogue that could display better pharmacokinetic properties and less side effects,deuterated plinabulin 9 was synthesized and evaluated in vitro and in vivo.In comparison with plinabulin,in vivo pharmacokinetic studies indicated that the deuterated derivative 9 could alter blood circulation behavior obviously,which was proved by increased area under the plasma concentration-time curve(AUC_(0–∞)),reduced clearance(CL),and prolonged total body mean residence time(MRT).The derivative 9 also has higher inhibition rates against Bx PC-3,Jurkat and A-431 tumor cell lines as compared with its prototype plinabulin.Therefore,the deuterated compound 9 might be developed as a potential agent for different cancer treatments.
