Blue‐Fluorescent Probes for Lipid Droplets Based on Dihydrochromeno‐Fused Pyrazolo‐ and Pyrrolopyridines

• Published in: European journal of organic chemistry Vol. 2018; no. 34; pp. 4795 - 4801
• Main Authors: Becerra‐Ruiz, Martín, Vargas, Victor, Jara, Patricio, Tirapegui, Cristian, Carrasco, Carlos, Nuñez, Marco, Lezana, Nicolás, Galdámez, Antonio, Vilches‐Herrera, Marcelo
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 16.09.2018; Wiley Subscription Services, Inc
• Subjects: Boron; Chemistry; Chemistry, Organic; Constraining; Diels–Alder reactions; Droplets; Dyes; Energy storage; Fluorescent indicators; Fluorescent probes; Fused‐ring systems; Lipids; Metabolic disorders; Nitrogen heterocycles; Organelles; Organic chemistry; Physical Sciences; Pyrazole; Pyrrolopyridines; Science & Technology; Staining; Visible spectrum; Diels-Alder reactions; RED; DESIGN; Fluorescent probes; DYES; Nitrogen heterocycles; PRODRUGS; PHOTOPHYSICS; Lipids; Fused-ring systems
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201701633

Lipid droplets (LDs) have been recognized as highly dynamic cellular organelles involved in important biological functions for the survival of organisms such as supplying food or energy. Nevertheless, lipid storage must be tightly controlled, because both its excess and the inability to store lipids can be detrimental to the organism, resulting in metabolic diseases or multifaceted systemic problems. Visualization and the monitoring of the concentration of LDs is essential to understanding these processes. Commercially available LD dyes, such as Nile Red and boron‐dipyrromethene (BODIPY), offer several advantageous characteristics, but can be limiting in multicolor imaging because most ready‐made fluorescent reporter constructs fluoresce in the green‐to‐red region of the visible spectrum. Nile Red emits between green and red, and BODIPY can be photoconverted from green to red fluorescence, limiting its ability to be utilized for time‐lapse imaging of living cells. Here, we report the design and synthesis, the photophysical characterization, and biological testing of two easily prepared series of new blue‐fluorescing dyes as markers for LDs. Confocal fluorescence microscopy results showed an interesting correlation between the chemical structures of these fluorescent probes and their specific staining patterns. The pyrazole‐based compound 11c was found to be a specific dye for LDs, whereas the pyrrole‐based compound 10d led to prominent staining of the membranous cell organelles. Fluorescent probes allow the observation, detection, and distribution of living objects in the intracellular space. Because lipid storage is associated with the pathogenesis of highly prevalent metabolic diseases, the detection of lipid droplets, a type of subcellular organelle, is important. Herein, the synthesis of two series of blue‐fluorescent probes is reported.