Cravotto Giancarlo, Balliano Gianni, Tagliapietra Silvia, Oliaro-Bosso Simonetta, Nano Gian Mario
Dipartimento di Scienza e Tecnologia del Farmaco, Università di Torino, Torino, Italy.
Chem Pharm Bull (Tokyo). 2004 Oct;52(10):1171-4. doi: 10.1248/cpb.52.1171.
Squalene-hopene cyclase (SHC) is a useful model enzyme for predicting molecular interactions with oxidosqualene cyclase (OSC). Structure--activity relationships were investigated for numerous coumarin-derived inhibitors of SHC, and structural simplifications are suggested. Both umbelliferone and 2,4-dihydroxyacetophenone provide convenient starting nuclei for the design of SHC inhibitors. Derivatives bearing an omega-epoxyfarnesyl moiety or just a plain alkyl chain showed an inhibitory effect on a recombinant SHC from Alicyclobacillus acidocaldarius expressed in Escherichia coli.
角鲨烯-藿烯环化酶（SHC）是用于预测与氧化角鲨烯环化酶（OSC）分子相互作用的一种有用的模型酶。研究了众多香豆素衍生的SHC抑制剂的构效关系，并提出了结构简化方案。伞形酮和2,4-二羟基苯乙酮都为SHC抑制剂的设计提供了便利的起始核心。带有ω-环氧法呢基部分或仅仅是普通烷基链的衍生物，对在大肠杆菌中表达的来自嗜酸嗜热栖热放线菌的重组SHC显示出抑制作用。
