1. N -Adamantyl-1-alkyl-4-oxo-1,4-dihydroquinoline-3-carboxamide Derivatives as Fluorescent Probes to Detect Microglia Activation through the Imaging of Cannabinoid Receptor Subtype 2 (CB2R).
- Author
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Intranuovo F, Majellaro M, Mastropasqua F, Delre P, Abatematteo FS, Mangiatordi GF, Stefanachi A, Brea J, Loza MI, Riganti C, Ligresti A, Kumar P, Esposito D, Cristino L, Nicois A, González L, Perrone MG, Colabufo NA, Sotelo E, Abate C, and Contino M
- Subjects
- Humans, Animals, Quinolines chemistry, Quinolines chemical synthesis, Adamantane analogs & derivatives, Adamantane chemistry, Adamantane chemical synthesis, Adamantane pharmacology, Ligands, Structure-Activity Relationship, Receptor, Cannabinoid, CB2 metabolism, Fluorescent Dyes chemistry, Fluorescent Dyes chemical synthesis, Microglia metabolism
- Abstract
Cannabinoid receptor subtype 2 (CB2R) is emerging as a pivotal biomarker to identify the first steps of inflammation-based diseases such as cancer and neurodegeneration. There is an urgent need to find specific probes that may result in green and safe alternatives to the commonly used radiative technologies, to deepen the knowledge of the CB2R pathways impacting the onset of the above-mentioned pathologies. Therefore, based on one of the CB2R pharmacophores, we developed a class of fluorescent N -adamantyl-1-alkyl-4-oxo-1,4-dihydroquinoline-3-carboxamide derivatives spanning from the green to the near-infrared (NIR) regions of the light spectrum. Among the synthesized fluorescent ligands, the green-emitting compound 55 exhibited a favorable binding profile (strong CB2R affinity and high selectivity). Notably, this ligand demonstrated versatility as its use was validated in different experimental settings such as flow cytometry saturation, competitive fluorescence assays, and in vitro microglia cells mimicking inflammation states where CB2R are overexpressed.
- Published
- 2024
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