The present study aimed at the development of fluorescent inhibitors addressing the GABA transporters mGAT1–mGAT4 as potential tool compounds in fluorescence based biological assays. The design of these fluorescent GAT inhibitors followed the structural motifs common for many GAT1–GAT4 inhibitors publicly known except that the lipophilic domain present in this compounds was replaced by a BODIPY moiety to serve as a fluorescent subunit. The fluorescent compounds obtained that way were tested for their inhibitory potencies and subtype selectivities at the four murine GABA transporter subtypes mGAT1–mGAT4 and for their binding affinity for mGAT1. All BODIPY derivatives displayed only low inhibitory potencies and subtype selectivities at the GABA transport proteins mGAT1–mGAT4, as well as low affinities for mGAT1. Still, compounds were found with reasonable binding affinities towards mGAT1 (pK_i ~ 5.0) and inhibitory potencies at mGAT2 and mGAT4 (pIC₅₀ ~ 5.0).

中文翻译：

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基于不对称取代BODIPY染料的荧光GAT配体的合成及生物学评价

本研究旨在开发针对GABA转运蛋白mGAT1-mGAT4的荧光抑制剂，将其作为基于荧光的生物学分析中潜在的工具化合物。这些荧光GAT抑制剂的设计遵循了许多广为人知的GAT1-GAT4抑制剂共有的结构基序，只是该化合物中存在的亲脂结构域被BODIPY部分取代，以充当荧光亚基。测试了以此方式获得的荧光化合物对四种鼠类GABA转运蛋白亚型mGAT1–mGAT4的抑制力和亚型选择性，以及它们对mGAT1的结合亲和力。所有BODIPY衍生物在GABA转运蛋白mGAT1–mGAT4上仅表现出低抑制力和亚型选择性，而对mGAT1的亲和力却很低。仍然，ķ_我 〜5.0），并在MGAT2和mGAT4（抑制能力的pIC ₅₀  〜5.0）。