The extensive applications of Firefly luciferase (Fluc) in numerous biological, biomedical, and clinical investigations rendered an urgent need for efficient and biocompatible Fluc inhibitors for the construction of novel assay platforms. Herein we describe the identification of 2-benzylidene-tetralone derivatives as highly potent and reversible Firefly luciferase inhibitors by competing with d-luciferin. The most active compound 48 was found to have >7000 fold higher potency (IC₅₀ = 0.25 nM) than that of the well-known luciferase inhibitor resveratrol (IC₅₀ = 1.9 μM) biochemically with sub- to low nanomolar IC₅₀ values, and it can efficiently block the Fluc generated bioluminescence in vivo.

中文翻译：

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2-亚苄基-四氢萘酮衍生物作为高效可逆萤火虫荧光素酶抑制剂的鉴定

萤火虫荧光素酶 (Fluc) 在众多生物学、生物医学和临床研究中的广泛应用使得迫切需要高效且生物相容的 Fluc 抑制剂来构建新型检测平台。在此，我们描述了通过与d -荧光素竞争将 2-亚苄基-四氢萘酮衍生物鉴定为高效且可逆的萤火虫荧光素酶抑制剂。发现最具活性的化合物48 的效力 (IC ₅₀ = 0.25 nM) 比众所周知的荧光素酶抑制剂白藜芦醇 (IC ₅₀ = 1.9 μM) 生物化学具有亚至低纳摩尔 IC ₅₀值高 > 7000 倍，并且能有效阻断体内Fluc产生的生物发光。