The first syntheses of GLA-60 positional isomers and their biological activities

Article abstract of DOI:10.1246/bcsj.70.1149

Six GLA-60 positional isomers (8, 14, 14', 20, 26, and 26') were synthesized to investigate their biological activities. Compound 8 exhibited potent agonistic activity, while compounds 26 and 26' exhibited slight agonistic activity on TNFα production toward human monoblastic U937 cells. TNFα production (% control; 10 ng ml^- of LPS = 100) of compound 8 in the concentration of 10 μM was 611, and that of lipid A in the same concentration was 651. In contrast, the difluorinated compounds 14, 14', and 20 showed little agonistic activity on TNFα production. And neither compound 8 nor compounds 26 and 26' showed antagonistic activity. On the other hand, the difluorinated compounds 14, 14', and 20 showed potent antagonistic activity, and inhibited the LPS-induced TNFα production dose-dependently. Compound 14' (10 μM) inhibited in excess of 80% of the LPS-induced TNFα production.