Secondary metabolites from marine cyanobacteria and algae inhibit LFA-1/ICAM-1 mediated cell adhesion.
An assay for inhibitors of LFA-1/ICAM-1 mediated cell-cell adhesion has been employed to identify new pharmacologically active compounds from marine cyanobacteria and algae. From a panel of sixty unusual marine natural products, seventeen compounds inhibited LFA-1/ICAM-1-based cell aggregation without showing significant cytotoxicity in the primary assay. Six compounds inhibited the cell-cell adhesion of HL-60 cells to CHO-ICAM-1 cells. The unusual oxylipin Cymathere aldehyde methyl ester (IC (50) 3.5 microM), cyanobacterial lipopeptides microcolins B (IC (50) 0.15 microM) and D (IC (50) 0.9 microM), bromophenol avrainvilleol (IC (50) 2.2 microM), sesquiterpene cymopol (IC (50) 2.7 microM), and cryptophyte derived compound styrylchromone hormothamnione diacetate (IC (50) 1.5 microM) significantly inhibited LFA-1/ICAM-1 mediated cell adhesion. The pharmacological activity and structure-activity relationships of selected marine algal metabolites are described. Abbreviations. LFA-1:Lymphocyte function-associated molecule-1 ICAM-1:Intercellular cell adhesion molecule-1 PMA:Phorbol 12-myristate 13-acetate HL-60:Promyelocytic human leukemia-60 CHO:Chinese hamster ovary
Takamatsu
Satoshi
S
National Center for Natural Products Research, Oregon 97331, USA. stakamat@olemiss.edu
Nagle
Dale G
DG
Gerwick
William H
WH
D000818:Animals; D001685:Biological Factors / Q000737:chemistry / Q000494:pharmacology*; D016466:CHO Cells / Q000187:drug effects / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology*; D002449:Cell Aggregation / Q000187:drug effects / Q000276:immunology*; D006224:Cricetinae; D003412:Cricetulus; D000458:Cyanobacteria / Q000737:chemistry*; D056890:Eukaryota / Q000737:chemistry*; D005260:Female; D018922:HL-60 Cells / Q000187:drug effects / Q000276:immunology; D006801:Humans; D020128:Inhibitory Concentration 50; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D013329:Structure-Activity Relationship
D001685:Biological Factors; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1