Molecular shape and pharmacological function are interconnected. To capture shape, the fractal dimensionality concept was employed, providing a natural similarity measure for the virtual screening of de novo generated small molecules mimicking the structurally complex natural product (−)‐englerin A. Two of the top‐ranking designs were synthesized and tested for their ability to modulate transient receptor potential (TRP) cation channels which are cellular targets of (−)‐englerin A. Intracellular calcium assays and electrophysiological whole‐cell measurements of TRPC4 and TRPM8 channels revealed potent inhibitory effects of one of the computer‐generated compounds. Four derivatives of this identified hit compound had comparable effects on TRPC4 and TRPM8. The results of this study corroborate the use of fractal dimensionality as an innovative shape‐based molecular representation for molecular scaffold‐hopping.

中文翻译：

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分形维数的形状相似度：在（-）-Englerin A模拟物从头设计中的应用。

分子形状和药理功能是相互联系的。为了捕获形状，采用了分形维数概念，为虚拟筛选从头生成的模仿结构复杂的天然产物（-）-englerin A的小分子提供了自然相似性度量。合成并测试了两个顶级设计调节瞬态受体电位（TRP）阳离子通道的能力，而阳离子通道是（-）-englerin A的细胞靶标。对TRPC4和TRPM8通道的细胞内钙测定和电生理全细胞测量表明，其中一种计算机产生的强抑制作用化合物。该鉴定出的命中化合物的四种衍生物对TRPC4和TRPM8具有可比的作用。