Cristiane F. da Costa

Preparation and antileishmanial activity of lipophilic N-alkyl diamines.

We report in this work the preparation and the in vitro antileishmanial activity of a series of long chains N-monoalkylated diamines and two pyridinediamine derivatives. Several compounds, tested for their in vitro antiproliferative activity against Leishmania amazonensis and Leishmania chagasi, displayed a good inhibition of parasite growth, with IC(50) below 10 microM. Compounds 10 (N-dodecyl-1,2-ethanediamine), 15 (N-decyl-1,3-propanediamine) and 20 (N-dodecyl-1,4-butanediamine) were 7.3, 2.6 and 3.6 times, respectively, more active than the reference drug amphotericin B against L. chagasi promastigote forms.

Impact of the carbon chain length of novel platinum complexes derived from N-alkyl-propanediamines on their cytotoxic activity and cellular uptake.

This work describes the synthesis and characterization of four new ligands derived from 1,3-propanediamine in addition to the preparation and characterization of their respective platinum(II) complexes by reaction with K(2)PtCl(4). These ligands were obtained by the reaction of the corresponding alkyl mesylate with 1,3-propanediamine. We have prepared compounds having different carbon chains lengths in an attempt to correlate this factor, which influences the lipophilicity of the compounds, with cytotoxic activity. Octanol/water partition coefficients, the effect of the four complexes on the growth of two tumoral cell lines, and their cellular uptake were investigated. Increasing lipophilicity enhances the rate of cellular uptake and, consequently, the cytotoxic activity.

Synthesis and Antileishmanial Activity of Lipidic Amino Alcohols

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 IC50 below 10 μm. Compound 11f was more active than the reference drug amphotericin B against L. chagasi promastigote forms.

Inhibiting AKT phosphorylation employing non-cytotoxic anthraquinones ameliorates TH2 mediated allergic airways disease and rhinovirus exacerbation.

Background Severe asthma is associated with T helper (TH) 2 and 17 cell activation, airway neutrophilia and phosphoinositide-3-kinase (PI3K) activation. Asthma exacerbations are commonly caused by rhinovirus (RV) and also associated with PI3K-driven inflammation. Anthraquinone derivatives have been shown to reduce PI3K-mediated AKT phosphorylation in-vitro. Objective To determine the anti-inflammatory potential of anthraquinones in-vivo. Methods BALB/c mice were sensitized and challenged with crude house dust mite extract to induce allergic airways disease and treated with mitoxantrone and a novel non-cytotoxic anthraquinone derivative. Allergic mice were also infected with RV1B to induce an exacerbation. Results Anthraquinone treatment reduced AKT phosphorylation, hypoxia-inducible factor-1α and vascular endothelial growth factor expression, and ameliorated allergen- and RV-induced airways hyprereactivity, neutrophilic and eosinophilic inflammation, cytokine/chemokine expression, mucus hypersecretion, and expression of TH2 proteins in the airways. Anthraquinones also boosted type 1 interferon responses and limited RV replication in the lung. Conclusion Non-cytotoxic anthraquinone derivatives may be of therapeutic benefit for the treatment of severe and RV-induced asthma by blocking pro-inflammatory pathways regulated by PI3K/AKT.

Preparation and antitubercular activity of lipophilic diamines and amino alcohols.

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.

Synthesis and Evaluation of Cytotoxicity and Inhibitory Effect on Nitric Oxide Production by J774A.1 Macrophages of New Anthraquinone Derivatives

Mitoxantrone is an anthracene-based anticancer agent whose efficacy in treating autoimmune diseases is believed to be due to cytotoxicity and inhibition of proliferation of cells. Several novel anthraquinone derivatives, analogs of mitoxantrone, were designed and synthesized. Lipophilic and functionalized mitoxantrone analogs were prepared by a simple methodology and the cytotoxicity and the inhibitory effect on nitric oxide release of these compounds were demonstrated in vitro on J774A.1 macrophages. Interestingly compounds 3, 4, 5, 6, 7, and 8 exhibited reduction in NO release (62.4%, 92.6%, 73.4%, 58.4%, 57.8% and 53.4%, respectively) in comparison to NG-n-methyl-arginine treated control, without cytotoxicity. In conclusion, anthraquinone derivatives were prepared in a good yield and showed promissory antiinflammatory properties.