Novel 1,8-Naphthalimide Derivatives As Antitumor Agents and Potent Demethylase Inhibitors.

ABSTRACT: Functional 1,8-naphthalimide derivatives are rapidly developing in the field of anticancer research. Herein, we designed and synthesized a series of naphthalimide derivatives with different substituents. Interestingly, 1,8-naphthalimide derivatives 1 and 7 inhibited a human demethylase FTO (the fat mass and obesity-associated protein). Computer simulation studies further indicated that 1 and 7 entered the FTO's structural domain II binding pocket through hydrophobic and hydrogen bonding interactions. Anticancer mechanism studies showed that 1 and 7 induced DNA damage and autophagic cell death in A549 cells. The high antiproliferative activity of 1 and 7 was further confirmed by 3D multicellular A549 tumor spheroid assays. This study f

SUBMITTER: Ge C 

PROVIDER: S-EPMC10641888 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature