Discovery of new fluorescent thiazole-pyrazoline derivatives as autophagy inducers by inhibiting mTOR activity in A549 human lung cancer cells.

ABSTRACT: A series of fluorescent thiazole-pyrazoline derivatives was synthesized and their structures were characterized by ¹H NMR, ¹³C NMR, and HRMS. Biological evaluation demonstrated that these compounds could effectively inhibit the growth of human non-small cell lung cancer (NSCLC) A549 cells in a dose- and time-dependent manner in vitro and inhibit tumor growth in vivo. The structure-activity relationship (SAR) of the compounds was analyzed. Further mechanism research revealed they could induce autophagy and cell cycle arrest while had no influence on cell necrosis. Compound 5e inhibited the activity of mTOR via FKBP12, which could be reversed by 3BDO, an mTOR activator and autophagy inhibitor. Compound 5e inhibited growth, promoted autophagy of A549 cells in vivo. Moreo

SUBMITTER: Lin Z 

PROVIDER: S-EPMC7371735 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature