Fungal pyrrolidine-containing metabolites inhibit alkaline phosphatase activity in bone morphogenetic protein-stimulated myoblastoma cells

作     者：Takashi Fukuda Ryuji Uchida Hiroyo Inoue Satoshi Ohte Hiroyuki Yamazaki Daisuke Matsuda Takenobu Katagiri Hiroshi Tomoda 

作者机构：Graduate School of Pharmaceutical SciencesKitasato UniversityTokyoJapan Research Center for Genomic MedicineSaitama Medical UniversitySaitamaJapan 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2012年第2卷第1期

页      面：23-27页

学科分类：1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 100210[医学-外科学(含：普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 10[医学] 

主　　题：Lucilactaenes Fungal metabolites C2C12 myoblasts Fibrodysplasia ossificans progressiva 

摘      要：Fibrodysplasia ossificans progressiva(FOP)is a rare autosomal dominant congenital disorder characterized by progressive heterotopic ossification in muscle tissues.A constitutively activated mutation of a bone morphogenetic protein(BMP)receptor,ALK2,has been identified in patients with *** report here that four structurally related compounds,lucilactaene,hydroxylucilactaene,NG-391 and NG-393,produced by fungal strain Fusarium sp.B88,inhibit BMP signaling in *** phosphatase activity,a marker enzyme of osteoblastic differentiation,was decreased in C2C12 myoblasts stably expressing mutant ALK2 by treatment with those compounds with IC_(50) values of 5.7,6.8,6.9 and 6.1 mM,***,NG-391 and NG-393 inhibited BMP-specific luciferase reporter activity,which is directly regulated by transcription factor Smads,with IC50 values of 1.4 and 2.1 mM,*** findings suggest that these fungal metabolites may provide a new direction in the development of FOP therapeutics.