title: Isolation and Structure Elucidation of Cytotoxic Saccharothriolides D to F from a Rare Actinomycete Saccharothrix sp. and Their Structure-Activity Relationship.
abstract: Three new 10-membered macrolides, saccharothriolides D-F (1-3), were isolated from a rare actinomycete, Saccharothrix sp. A1506. The planar structures were determined from analysis of extensive NMR and HR-ESI-MS data, and the absolute configurations were established by ECD spectroscopy analysis. Saccharothriolides D (1) and E (2) were determined to be C-2 epimers of saccharothriolides A (4) and B (5), respectively. Saccharothriolide F (3) was identified to be a demethylated congener of saccharothriolides D (1) and A (4) at the C-2 position. The availability of compounds 1-6 enabled a structure-activity relationship study that revealed the importance of the phenolic hydroxy group at C-2″ and the stereochemistry of C-2 for the inhibition of human fibrosarcoma HT1080 cell growth.
authors.affiliation: Department of System Chemotherapy and Molecular Sciences, Division of Bioinformatics and Chemical Genomics, Graduate School of Pharmaceutical Sciences, Kyoto University , Kyoto 606-8501, Japan.
authors.forename: Shan
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of System Chemotherapy and Molecular Sciences, Division of Bioinformatics and Chemical Genomics, Graduate School of Pharmaceutical Sciences, Kyoto University , Kyoto 606-8501, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nishimura
authors.affiliation: Bioresource Laboratories, MicroBioPharm Japan Co., Ltd. (MBJ) , Iwata, Shizuoka 438-0078, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Ito
authors.affiliation: Bioresource Laboratories, MicroBioPharm Japan Co., Ltd. (MBJ) , Iwata, Shizuoka 438-0078, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Tsuchida
authors.affiliation: Department of System Chemotherapy and Molecular Sciences, Division of Bioinformatics and Chemical Genomics, Graduate School of Pharmaceutical Sciences, Kyoto University , Kyoto 606-8501, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kakeya
mesh_terms: D000192:Actinomycetales / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D018942:Macrolides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D018942:Macrolides; C000618134:saccharothriolide D; C000618135:saccharothriolide E; C000618136:saccharothriolide F