title: Structure-activity relationship studies on acremomannolipin A, the potent calcium signal modulator with a novel glycolipid structure 4: Role of acyl side chains on d-mannose.
abstract: As part of an ongoing study on the structure-activity relationship of acremomannolipin A (1)-the novel glycolipid isolated from Acremonium strictum possessing potent calcium signal-modulating activity-the role of acyl substituents on the d-mannose moiety was examined. Three partially deacylated homologs (2a-2c) and 20 homologs (2d-2w) bearing different acyloxy side chains were synthesized via the stereoselective β-mannosylation of appropriately protected mannosyl sulfoxides (3) with d-mannitol derivatives (4), and their calcium signal-modulating activities were examined. The activities of 2a-2c were completely lost. Homologs bearing relatively short acyloxy groups at C-3, C-4, and C-6 positions (2t-2v) exhibited less activity than 1, whereas a heptanoyl homolog (2w: C7) maintained activity nearly equal to that of 1. When the acyl groups at these three positions were substituted by an octanoyl group (2i: C8), the activity was completely lost. On the other hand, of the 10 homologs in which the octanoyl at C-2 was substituted by other acyloxy moieties (2j-2s), three (2m: C7, 2n: C9, 2o: C10) maintained potent activity. These results suggested that peracylated mannose structure is critical for calcium signal-modulating activity, and this activity is precisely dependent on the length of four acyl side chains on d-mannose.
authors.affiliation: Laboratory of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Tsutsui
authors.affiliation: Laboratory of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.
authors.forename: Genzoh
authors.initials: G
authors.lastname: Tanabe
authors.affiliation: Laboratory of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.
authors.forename: Nami
authors.initials: N
authors.lastname: Ikeda
authors.affiliation: Laboratory of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.
authors.forename: Saika
authors.initials: S
authors.lastname: Okamura
authors.affiliation: Laboratory of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.
authors.forename: Marika
authors.initials: M
authors.lastname: Ogawa
authors.affiliation: Laboratory of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.
authors.forename: Kuniko
authors.initials: K
authors.lastname: Miyazaki
authors.affiliation: Laboratory of Molecular Pharmacogenomics, Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Kita
authors.affiliation: Laboratory of Molecular Pharmacogenomics, Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan. Electronic address: sugiurar@phar.kindai.ac.jp.
authors.forename: Reiko
authors.initials: R
authors.lastname: Sugiura
authors.affiliation: Laboratory of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan. Electronic address: muraoka@phar.kindai.ac.jp.
authors.forename: Osamu
authors.initials: O
authors.lastname: Muraoka
mesh_terms: D001681:Biological Assay; D020013:Calcium Signaling / Q000187:drug effects*; D006017:Glycolipids / Q000737:chemistry* / Q000494:pharmacology*; D008358:Mannose / Q000737:chemistry*; D012568:Schizosaccharomyces / Q000166:cytology / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D006017:Glycolipids; C579014:acremomannolipin A; D008358:Mannose
keywords: Acremomannolipin A; Acremonium strictum; Calcium signal modulator; Glycolipid; SAR study