title: Synthesis and biological evaluation of quinaldopeptin.
abstract: The second-generation total synthesis of quinaldopeptin (1) was established via a Staudinger/aza-Wittig/diastereoselective Ugi three-component reaction sequence and a racemization-free [5 + 5] coupling and macrolactamization. A single-crystal X-ray structure of the chromophore analogue 26 confirmed the structural and stereochemical assignments of the macrocycle. Synthetic 1 successfully unwound supercoiled DNA to form a relaxed DNA in a dose-dependent manner, the binding affinity of 1 to four dsODNs was within a similar range (K(b) = 1.45-2.53 × 10(7) M(-1)), and the sequence selectivity was subtle. It was suggested that 1 possesses biological behaviors similar to those of sandramycin (2) in terms of cytotoxic activity against human cancer cell lines (IC50 = 3.2-12 nM) and HIF-1 inhibitory activity.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University , Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Katsushi
authors.initials: K
authors.lastname: Katayama
authors.forename: Takuya
authors.initials: T
authors.lastname: Okamura
authors.forename: Takuya
authors.initials: T
authors.lastname: Sunadome
authors.forename: Koji
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeda
authors.forename: Motoo
authors.initials: M
authors.lastname: Shiro
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ichikawa
mesh_terms: D002460:Cell Line; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000187:drug effects; D004448:Echinomycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology
chemical_list: D051793:Hypoxia-Inducible Factor 1; D010456:Peptides, Cyclic; C063090:sandramycin; C065444:quinaldopeptin; D004448:Echinomycin; D004247:DNA