Design, synthesis, and evaluation of nile red analogs for myelin imaging as near-infrared fluorescence probe

Abstract

Myelination is a fundamental biological process in the vertebrate nervous system. Direct detection and quantification of myelin content in vivo can facilitate diagnosis and therapeutic treatment of myelin-related diseases such as multiple sclerosis. Over the past decade, a series of myelin-specific molecule probes with stilbene structural frame have been developed. Herein, a class of novel Nile Red analogs containing the structure feature similar to stilbene have been designed and synthesized. Their structures were confirmed by 1H NMR, 13C NMR, and HRMS analyses. All of them fluoresce in the near-infrared range with emission wavelengths ranging from 651 nm to 691 nm. In vitro assays revealed that these compounds can specifically bind to myelinated fibers and 9-diethylamino-1-methylamino-5H-benzo[a]phenoxazin-5-one (20, 1-MeNHNR) was screened as lead compound. Ex vivo imaging and in vivo near-infrared fluorescence (NIRF) imaging demonstrated that 1-MeNHNR is a promising NIRF probe for myelin imaging.