Rational Design of a Highly Sensitive Carboxylesterase Probe and Its Application in High-Throughput Screening for Uncovering Carboxylesterase Inhibitors.
J Org Chem
; 2024 May 08.
Article
in En
| MEDLINE
| ID: mdl-38720168
ABSTRACT
Tracking carboxylesterases (CESs) through noninvasive and dynamic imaging is of great significance for diagnosing and treating CES-related metabolic diseases. Herein, three BODIPY-based fluorescent probes with a pyridine unit quaternarized via an acetoxybenzyl group were designed and synthesized to detect CESs based on the photoinduced electron transfer process. Notably, among these probes, BDPN2-CES exhibited a remarkable 182-fold fluorescence enhancement for CESs within 10 min. Moreover, BDPN2-CES successfully enabled real-time imaging of endogenous CES variations in living cells. Using BDPN2-CES, a visual high-throughput screening method for CES inhibitors was established, culminating in the discovery of an efficient inhibitor, WZU-13, sourced from a chemical library. These findings suggest that BDPN2-CES could provide a new avenue for diagnosing CES-related diseases, and WZU-13 emerges as a promising therapeutic candidate for CES-overexpression pathological processes.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
J Org Chem
Year:
2024
Document type:
Article