title: Concise synthesis of a probe molecule enabling analysis and imaging of vizantin.
abstract: Trehalose 6,6'-dicorynomycolate (TDCM) was first characterized in 1963 as a cell surface glycolipid of Corynebacterium spp. by Ioneda and co-workers. TDCM shows potent anti-tumor activity due to its immunoadjuvant properties. Furthermore, the toxicity of TDCM in mice is much weaker than the related trehalose diester of mycolic acid; trehalose 6,6'-dimycolate (TDM, formerly known as cord factor). We have investigated the chemical modification of this class of compound to generate novel agents that display increased immunoadjuvant activity with minimal associated toxicity. During the course of this work we recently developed 6,6'-bis-O-(3-nonyldodecanoyl)-α,α'-trehalose (designated as vizantin). Our results show that vizantin exhibited a potent prophylactic effect on experimental lung metastasis of B16-F0 melanoma cells without a loss of body weight and death in mice. Furthermore, vizantin effectively stimulated human macrophages in an in vitro model, making it a promising candidate for a safe adjuvant in clinical applications. In order to elucidate the pharmacokinetics of vizantin, a probe molecule with similar activity was developed on the basis of a structure-activity relationship (SAR) study with vizantin. The distribution of the probe molecule after intravenous administration into a mouse was assessed by macro confocal microscopy, where it was found to accumulate in the lungs and liver.
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima, Japan. hirofumi@ph.bunri-u.ac.jp
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Masataka
authors.initials: M
authors.lastname: Oda
authors.forename: Mayo
authors.initials: M
authors.lastname: Nakano
authors.forename: Kenta
authors.initials: K
authors.lastname: Yabiku
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shibutani
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Nakanishi
authors.forename: Midori
authors.initials: M
authors.lastname: Suenaga
authors.forename: Masahisa
authors.initials: M
authors.lastname: Inoue
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Imagawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nagahama
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Matsunaga
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Himeno
authors.forename: Kojun
authors.initials: K
authors.lastname: Setsu
authors.forename: Jun
authors.initials: J
authors.lastname: Sakurai
authors.forename: Mugio
authors.initials: M
authors.lastname: Nishizawa
mesh_terms: D000276:Adjuvants, Immunologic / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D002460:Cell Line; D054407:Chemokine CCL4 / Q000378:metabolism; D003352:Corynebacterium / Q000737:chemistry; D006017:Glycolipids / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008546:Melanoma, Experimental / Q000473:pathology; D051379:Mice; D015335:Molecular Probes / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D014199:Trehalose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C579729:6,6'-bis-O-(3-nonyldodecanoyl)-alpha,alpha'-trehalose; D000276:Adjuvants, Immunologic; D054407:Chemokine CCL4; D006017:Glycolipids; D015335:Molecular Probes; D014409:Tumor Necrosis Factor-alpha; D014199:Trehalose