Author/Authors :
Miyako Masubuchi، نويسنده , , Ken-ichi Kawasaki، نويسنده , , Hirosato Ebiike، نويسنده , , Yoshihiko Ikeda، نويسنده , , Shinji Tsujii، نويسنده , , Satoshi Sogabe، نويسنده , , Toshihiko Fujii، نويسنده , , Kiyoaki Sakata، نويسنده , , Yasuhiko Shiratori، نويسنده , , Yuko Aoki، نويسنده , , Tatsuo Ohtsuka، نويسنده , , Nobuo Shimma، نويسنده ,
Abstract :
Potent and selective Candida albicans N-myristoyltransferase (CaNmt) inhibitors have been identified through optimization of a lead compound 1 discovered by random screening. The inhibitor design is based on the crystal structure of the CaNmt complex with compound (S)-3 and structure–activity relationships (SARs) have been clarified. Modification of the C-4 side chain of 1 has led to the discovery of a potent and selective CaNmt inhibitor 11 (RO-09-4609), which exhibits antifungal activity against C. albicans in vitro.
