Secondary Metabolites from Marine Cyanobacteria and Algae Inhibit LFA-1/ICAM-1 Mediated Cell Adhesion

Abstract

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 (IC₅₀ 3.5 μM), cyanobacterial lipopeptides microcolins B (IC₅₀ 0.15 μM) and D (IC₅₀ 0.9 μM), bromophenol avrainvilleol (IC₅₀ 2.2 μM), sesquiterpene cymopol (IC₅₀ 2.7 μM), and cryptophyte derived compound styrylchromone hormothamnione diacetate (IC₅₀ 1.5 μM) 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

Cell adhesion - cell aggregation - LFA-1 - ICAM-1 - cyanobacteria - algae - marine natural products - HL-60 cell - chinese hamster ovary cell

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