Novel water-soluble prodrugs of combretastatin A-4 （5-8） were synthesized and evaluated for their in vitro cytotoxicity against lung carcinoma A549. Compound 5, bearing phosphoryl choline （PC） moiety, showed 90% i...Novel water-soluble prodrugs of combretastatin A-4 （5-8） were synthesized and evaluated for their in vitro cytotoxicity against lung carcinoma A549. Compound 5, bearing phosphoryl choline （PC） moiety, showed 90% inhibition at 32 ktg/mL concentration after 24 h. The findings showed the PC derivative would be a promising candidate for the development of new water-soluble prodrug of cytotoxic combretastatin A-4,展开更多
Herein a series of combretastatin A-4(CA-4)analogues with aggregation-induced emission characteristics(compounds a1-a19)were rationally designed and synthesized.The research results showed that the mechanism of AIE of...Herein a series of combretastatin A-4(CA-4)analogues with aggregation-induced emission characteristics(compounds a1-a19)were rationally designed and synthesized.The research results showed that the mechanism of AIE of a1-a19 could be attributed to the dual function of the restriction of intramolecular motion(RIM)and J-aggregate formation.Furthermore,the detailed investigation on the action mechanisms revealed that a19 diffused from lysosomes into the cytoplasm,and then targeted the colchicine binding site to induce cell cycle arrest and apoptosis in cancer cells.These results provide new ideas and impetus for the rational design of CA-4 analogues.展开更多
文摘Novel water-soluble prodrugs of combretastatin A-4 （5-8） were synthesized and evaluated for their in vitro cytotoxicity against lung carcinoma A549. Compound 5, bearing phosphoryl choline （PC） moiety, showed 90% inhibition at 32 ktg/mL concentration after 24 h. The findings showed the PC derivative would be a promising candidate for the development of new water-soluble prodrug of cytotoxic combretastatin A-4,
基金supported by the National Key R&D Programs of China(2017YFC1103603)the National Natural Science Foundation of China(21877049,32171296)+2 种基金Guangdong Natural Science Foundation(2020B1515120043)the Innovation Team Project in Guangdong Colleges and Universities(2019KCXTD008)K.C.Wong Education Foundation。
文摘Herein a series of combretastatin A-4(CA-4)analogues with aggregation-induced emission characteristics(compounds a1-a19)were rationally designed and synthesized.The research results showed that the mechanism of AIE of a1-a19 could be attributed to the dual function of the restriction of intramolecular motion(RIM)and J-aggregate formation.Furthermore,the detailed investigation on the action mechanisms revealed that a19 diffused from lysosomes into the cytoplasm,and then targeted the colchicine binding site to induce cell cycle arrest and apoptosis in cancer cells.These results provide new ideas and impetus for the rational design of CA-4 analogues.
