Nucleus-targeting imaging and enhanced cytotoxicity based on naphthalimide derivatives

Bioorg Chem. 2021 Jul 20;115:105188. doi: 10.1016/j.bioorg.2021.105188. Online ahead of print.ABSTRACTOrganelles possess critical biological effects in cellular processes. However, the relationship between organelle targeting and antitumour activity is a challenging issue. In this paper, a number of amide/acylhydrazine modified naphthalimide derivatives were designed and synthesized. Interestingly, amide modified naphthalimide derivatives NI-A-NH and NI-C-NH with (R)-piperdine and (S)-pyrrolidine functionalization exhibited enhanced cytotoxicity compared with acylhydrazine modified derivatives NI-A-2NH and NI-C-2NH. However, acylhydrazine modified derivatives NI-B-2NH and NI-D-2NH with (S)-piperdine and achiral piperdine conjugates possessed better cytotoxicity than NI-B-NH and NI-D-NH with amide modifications. Fluorescence imaging, DNA binding interactions and cell cycle analyses were further completed to clarify that the nucleus-targeting effects showed enhanced cytotoxic activity, strong DNA binding and the blocking of cells in S phase. These results provide a preliminary theoretical basis for the further design of organelle-targeting antitumour drugs.PMID:34314915 | DOI:10.1016/j.bioorg.2021.105188

Source: Bioorganic Chemistry - July 27, 2021 Category: Chemistry Authors: Shan-Shan Wang Shao-Ying Du Xu He Yu-Ming Qi Xiao-Liu Li Rui-Xue Rong Zhi-Ran Cao Ke-Rang Wang Source Type: research