ABSTRACT
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-1ß. 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-ß 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-1ß 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.
Subject(s)
Amino Alcohols/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Edema/drug therapy , Hypersensitivity, Delayed/drug therapy , Allergens , Amino Alcohols/pharmacology , Animals , Anti-Inflammatory Agents/pharmacology , Carrageenan , Cell Line , Cells, Cultured , Edema/chemically induced , Edema/immunology , Foot , Hypersensitivity, Delayed/immunology , Interleukin-1beta/immunology , Lipopolysaccharides , Macrophages/drug effects , Macrophages/immunology , Male , Mice , Mice, Inbred BALB C , Nitric Oxide/metabolism , Ovalbumin , Tumor Necrosis Factor-alpha/immunologyABSTRACT
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 µg/mL), while the galactopyranoside derivative 8d showed a notable nitric oxide inhibitory activity (126% at 0.5 µg/mL).
Subject(s)
Amino Alcohols/chemistry , Carbohydrates/chemistry , Nitric Oxide/metabolism , Amino Alcohols/chemical synthesis , Amino Alcohols/toxicity , Animals , Arabinose/chemistry , Cell Line, Tumor , Galactose/chemistry , Glucose/chemistry , Interferon-gamma/pharmacology , Lipopolysaccharides/pharmacology , MiceABSTRACT
In this work, a number of lipidic amino alcohols wereas synthesized and evaluated in vitro on cultures of Leishmania amazonensis and Leishmania chagasi. Nine amino alcohols showed inhibition of L. chagasi growth, and seven of them showed inhibition of L. amazonensis with IC(50) below 10 microm. Compound 11f was more active than the reference drug amphotericin B against L. chagasi promastigote forms.
Subject(s)
Amino Alcohols/chemical synthesis , Leishmania/drug effects , Trypanocidal Agents/chemical synthesis , Amino Alcohols/chemistry , Amino Alcohols/pharmacology , Amphotericin B/pharmacology , Humans , Leishmania/growth & development , Trypanocidal Agents/chemistry , Trypanocidal Agents/pharmacologyABSTRACT
A series of diamines and amino alcohols derived from 1-dodecanol, 1-tetradecanol, 1,2-dodecanediol and 1,2-tetradecanediol were synthesized and tested for their antitubercular activity. Compounds 3, 8 and 9 were found to be the most active (MIC of 6.25 microg/mL). Nine other compounds displayed activity against Mycobacterium tuberculosis, with a MIC of 12.5 microg/mL.
Subject(s)
Amino Alcohols/pharmacology , Antitubercular Agents/pharmacology , Diamines/pharmacology , Mycobacterium tuberculosis/drug effects , Amino Alcohols/chemical synthesis , Antitubercular Agents/chemistry , Diamines/chemical synthesis , Microbial Sensitivity TestsABSTRACT
In this work, we report the preparation and evaluation of the in vitro and in vivo of the immunosuppressive activity of a series of lipophilic amino alcohols and diamines. All compounds were evaluated for inhibition of cell proliferation, cytotoxicity and NO production. Compounds 9, 12, 13, 17, and 18 did not display inhibition of cell proliferation while decreased NO production. The two most potent compounds, 13 and 17, submitted to delayed-type hypersensitivity assays showed immunosuppressive activity.
Subject(s)
Amino Alcohols/pharmacology , Diamines/pharmacology , Immunosuppressive Agents/pharmacology , Amino Alcohols/chemical synthesis , Amino Alcohols/toxicity , Animals , Cells, Cultured , Diamines/chemical synthesis , Diamines/toxicity , Hypersensitivity, Delayed/chemically induced , Immunosuppressive Agents/chemical synthesis , Immunosuppressive Agents/toxicity , MiceABSTRACT
A series of N- and C-alkylated amino alcohols and of their protected galactopyranosyl derivatives was synthesized and evaluated for antitubercular activity. Five of these compounds displayed good activity, with a MIC below 12.5mug/mL. The presence of the carbohydrate slightly affected the antibacterial activity.
