Discovery of halogenated eurypamide B analogues as inhibitors of lipid droplet accumulation in macrophages

Bioorganic and Medicinal Chemistry Letters

Volumn 15, Issue 19, 2005, Pages 4189-4191

  Obata, Rika ^a   Ohshiro, Taichi ^b   Tomoda, Hiroshi ^b   Nishiyama, Shigeru ^a  

^a KEIO UNIVERSITY   (Japan)

^b KITASATO UNIVERSITY   (Japan)

Author keywords

Antiatherosclerotic agents; Cyclic isodityrosine; Eurypamide; Lipid droplet accumulation inhibitor; Thallium(III) oxidation

Indexed keywords

EURYPAMIDE B; FAT DROPLET; NATURAL PRODUCT; TRIPEPTIDE; TYROSINE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CONTROLLED STUDY; CYTOTOXICITY; DRUG ACTIVITY; DRUG EFFECT; DRUG SCREENING; DRUG SYNTHESIS; HALOGENATION; IC 50; MACROPHAGE; MOUSE; NONHUMAN;

ANIMALS; BIOLOGICAL PRODUCTS; HALOGENS; INHIBITORY CONCENTRATION 50; LIPID METABOLISM; LIPIDS; MACROPHAGES, PERITONEAL; MICE; MODELS, MOLECULAR; MOLECULAR STRUCTURE; OLIGOPEPTIDES; PEPTIDES, CYCLIC; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 23944450117     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.06.070     Document Type: Article

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13. Calculations were done using SPRTAN'02 for Macintosh (Wavefunction Inc., CA, USA) on a Power Mac G5 (Apple Computer Inc., CA, USA) computer. Halogenated 1 and halogen-free 2 model structures of the tripeptide bonds were generated as β-sheet conformation, then the tyrosine moiety was cyclized to construct an isodityrosine bond, and the models were pre-minimized. The stable local minimum conformers were distributed based on molecular mechanics calculations with MMFF94 force field. The first 20 stable minimum conformers were aligned at the residue of the DOPA moiety as shown in Figure 1. Decrease of conformational heterogeneity of the diaryl ether moiety and peptide chain linkage was observed in 1 compared to 2.
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16. None of the tested compounds showed antimicrobial activity. Antimicrobial activity was tested against Bacillus subtilis, Escherichia coli, Candida albicans, Staphylococcus aureus, Micrococcus luteus, Bacteroides fragilis, Acholeplasma laidlawii, Pyricularia oryzae, Aspergillus niger, Mucor racemosus, Saccharomyces cerevisiae, and Pseudomonas aeruginosa at 10 μg/6 mm diameter paper disks.