title: Isomethoxyneihumicin, a new cytotoxic agent produced by marine Nocardiopsis alba KM6-1.
abstract: A new cytotoxic agent designated isomethoxyneihumicin (1 and 2), a mixture of lactam-lactim tautomers, was isolated along with methoxyneihumicin (3) from the culture broth of the marine Nocardiopsis alba KM6-1. The structures of 1 and 2 were elucidated in spectroscopic analyses (1D and 2D NMR data, and ROESY correlations). Isomethoxyneihumicin (15.0 μM) and 3 (15.0 μM) arrested the cell cycle of Jurkat cells at the G2/M phase (66 and 67%) in 12 h. Isomethoxyneihumicin and 3 exhibited cytotoxicity against Jurkat cells with IC50values of 6.98 and 30.5 μM in 20 h, respectively. These results strongly suggest that isomethoxyneihumicin and 3 exhibit cytotoxicity against Jurkat cells by inhibiting the cell cycle at the G2/M phase.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Fukuda
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Misaki
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Nagai
authors.affiliation: Graduate School of Marine Science and Technology, Tokyo University of Marine Science and Technology, Tokyo, Japan.
authors.forename: Enjuro
authors.initials: E
authors.lastname: Harunari
authors.affiliation: Graduate School of Marine Science and Technology, Tokyo University of Marine Science and Technology, Tokyo, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Imada
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tomoda
mesh_terms: D000192:Actinomycetales / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D019169:Jurkat Cells; D007769:Lactams / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D011719:Pyrazines / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D007769:Lactams; D011719:Pyrazines; C000620672:isomethoxyneihumicin