title: Studies on novel bacterial translocase I inhibitors, A-500359s. III. Deaminocaprolactam derivatives of capuramycin: A-500359 E, F, H; M-1 and M-2.
abstract: Novel derivatives of capuramycin were obtained when 10 mM of 2-aminoethyl-L-cysteine (AEC), an inhibitor of aspartokinase, was added to the culture of Streptomyces griseus SANK 60196, the producer of A-500359. They were purified from the culture filtrate and their chemical structures were elucidated as a deaminocaprolactam derivative of capuramycin designated as A-500359 F, A-500359 E, a methyl ester of A-500359 F, and A-500359 H, a 3'-demethyl derivative of A-500359 F. Two other compounds, A-500359 M-1 and A-500359 M-2, were purified from the same medium and their structures were elucidated. A-500359 E, F, H, M-1 and M-2 inhibited bacterial translocase I with an IC50 of 0.027 microM, 1.1 microM, 0.008 microM, 0.058 microM and 0.010 microM, respectively. A-500359 E, M-1 and M-2 inhibited the growth of mycobacteria as well.
authors.affiliation: Lead Discovery Laboratories, Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Muramatsu
authors.forename: Shunichi
authors.initials: S
authors.lastname: Miyakoshi
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohnuki
authors.forename: Michiko Miyazawa
authors.initials: MM
authors.lastname: Ishii
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Arai
authors.forename: Toshio
authors.initials: T
authors.lastname: Takatsu
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Inukai
mesh_terms: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001381:Azepines / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000201:enzymology*; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013056:Spectrophotometry, Ultraviolet; D017855:Transferases (Other Substituted Phosphate Groups) / Q000037:antagonists & inhibitors*; D014529:Uridine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001381:Azepines; D004791:Enzyme Inhibitors; C049983:capuramycin; D017855:Transferases (Other Substituted Phosphate Groups); C100130:phospho-N-acetylmuramoyl pentapeptide transferase; D014529:Uridine