Acetyl-CoA carboxylase (ACC), a critical enzyme in the regulation of fatty acid synthesis and metabolism, has emerged as an attractive target for a plethora of emerging diseases, such as diabetes mellitus, nonalcoholic fatty liver disease, cancer, bacterial infections and so on. With decades of efforts in medicinal chemistry, significant progress has been made toward the design and discovery of a considerable number of inhibitors of this enzyme. In this review, we not only clarify the role of ACC in emerging diseases, but also summarize recent developments of potent ACC inhibitors and discuss their molecular mechanisms of action and potentials as novel drugs as well as future perspectives toward the design and discovery of novel ACC inhibitors.
Hypochlorite (ClO − ) and peroxynitrite (ONOO − ) are two crucial highly reactive oxygen/nitrogen species, which interplay with each other, and are implicated in numerous pathophysiological processes. The simultaneous detection of ClO − and ONOO − is immensely significant in evaluating the occurrence and progress of related diseases. Herein, a dualresponsive ratiometric fluorescent probe PTZ-H for the separate and simultaneous detection of ClO − and ONOO − was designed and synthesized. In this probe, the phenothiazine-based coumarin moiety was chosen as the ClO − responsive fluorescent fragment, and the precursor of 2-(benzo[d]thiazol-2-yl)aniline was employed as the sensor for ONOO − . The PTZ-H emitted red fluorescence (640 nm) can switch to green (520 nm) and turn on blue fluorescence (450 nm) in response to ClO − and ONOO − , respectively. This allowed the specific recognition and ratiometric quantification of ClO − and ONOO − with the detection limits of 17 and 21 nM, respectively. Notably, confocal laser scanning microscopy revealed that the PTZ-H probe could target-specifically image ClO − and ONOO − in living RAW 264.7 cells, zebrafish, and tissues with distinct fluorescence signals. With the aid of this single fluorescent probe, the endogenous accumulation of ClO − and ONOO − in inflammatory RAW 264.7 cells and zebrafish can be monitored through two distinct emission channels with fast responses. Moreover, the large fluorescence signal interval, high selectivity, and good biocompatibility may enable its application in deciphering the distribution and correlation of ClO − and ONOO − engaged in biological activity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.