The inflammation process is a coordinated response of the organism related to immune response with release of pro-inflammatory substances, as nitric oxide, TNF-α and IL-1β. In this work, a series of lipophilic amino alcohols were evaluated on RAW264.7 and primary macrophages for the modulation of nitric oxide and TNF-α. The most potent compounds were submitted to the treatment of BALB/c mice and evaluation of the carrageenan-induced paw edema and TNF-α and IL1-β release in the paws and anti-OVA delayed type hypersensitivity reaction. RAW264.7 and primary macrophages were incubated in the presence of amino alcohols at different concentrations (1, 0.5, 0.05 and 0.005 μg mL(-1)). All tested compounds were not cytotoxic, however the inhibition of NO and TNF-α were observed only in RAW264.7 cultures. The NO production were reduced in 100% for all compounds, but only the compounds 4a and 4b expressively reduced the TNF-α release (67% and 92% respectively). On the carrageenan-induced paw edema, the compound 4b treatment showed reduction of edema, TNF-α and IL-1β as efficient as dexamethasone treatment. Meanwhile, the compound 4a treatment showed only slight reduction of paw edema. In the anti-OVA DTH reaction, both compounds showed reduction in the paw edema as effective as dexamethasone. In function of the observed results in vitro and in the acute and anti-OVA inflammation of mice paw edema compound 4b showed promissory anti-inflammatory properties.

This work reports the preparation of several amino alcohols condensed with D-arabinose, D-glucose, and D-galactose derivatives. These compounds were evaluated in vitro for their cytotoxicity and ability to decrease nitric oxide production in J774A.1 cells. Arabinofuranoside derivatives 5a, 5b and 5c showed a significant inhibition of nitric oxide production (>80% at 5 lg ⁄ mL), while the galactopyranoside derivative 8d showed a notable nitric oxide inhibitory activity (126% at 0.5 lg ⁄ mL).

A series of diamines and amino alcohols derived from 1-dodecanol, 1-tetradecanol, 1,2-dodecanediol and 1,2-tetradecanediol

Mitoxantrone is an anthracenedione antineoplastic and immunosuppressive agent approved for multiple sclerosis treatment. Novel mono- and disubstituted anthraquinone derivatives, analogues of mitoxantrone, were synthesized through the addition of lipophilic amino alcohols and evaluated for their effect on IL-1β, TNF-α and nitric oxide production by LPS/IFN-γ-stimulated RAW264.7 cells. The disubstituted 1,4-anthracene-9,10-dione 10 showed significant inhibition of nitric oxide, TNF-α and IL-1β production at the concentration of 5 μg/mL, with a much lower cytotoxicity than mitoxantrone. The monosubstituted 3, 4, 11, 12 and 13 also displayed a moderate to good inhibitory capacity on IL-1β production. However, the methylated compounds 11, 12 and 13 failed to inhibit the TNF-α production, and compound 13 was the only one to decrease the production of nitric oxide. None of these derivatives was toxic at the tested concentrations. Compounds 10 and 13 had better inhibitory capacity of the inflammatory mediators analyzed, with reliable viability of the cells.

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