Synthesis and evaluation of a difluoromethylene analogue of sphingomyelin as an inhibitor of sphingomyelinase.

Abstract

A sphingomyelin analogue 2, in which the long alkenyl chain and the phosphodiester moiety of sphingomyelin were replaced by a phenyl and an isosteric difluoromethylenephosphonic acid, was prepared to evaluate its inhibitory potency to sphingomyelinase. The analogue non-competitively inhibited the neutral sphingomyelinase in bovine brain microsomes with an IC50 of 400 microM. The compound had the ability to suppress tumor necrosis factor alpha-induced apoptosis of PC-12 neurons at a low concentration of 0.1 microM.

Cite this paper

@article{Yokomatsu2001SynthesisAE, title={Synthesis and evaluation of a difluoromethylene analogue of sphingomyelin as an inhibitor of sphingomyelinase.}, author={Tsutomu Yokomatsu and Hiroko Takechi and Tatsuya Akiyama and Shiroshi Shibuya and Toshimi Kominato and Shinji Soeda and Hiroshi Shimeno}, journal={Bioorganic & medicinal chemistry letters}, year={2001}, volume={11 10}, pages={1277-80} }