Silvia Helena Cardoso

Fluoroquinolones: an important class of antibiotics against tuberculosis.

Tuberculosis (TB) is a global health problem due to the lack of new drugs in the market and also due to the advent of multidrug resistant strains (MDR). This disease affects around 8 million people and kills almost 3 million people each year and it is estimated that there are 1 billion infected with TB worldwide. Due to this problem fluoroquinolones have attracted much attention as the new class of anti TB drugs due to their fewer toxic side effects, improved pharmacokinetic properties and extensive and potent activity against Gram-positive and Gram-negative bacteria, including resistant strains. In this present review we report fluoroquinolones as a promising new class of anti TB.

Synthesis of 2-mercaptobenzothiazole and 2-mercaptobenzimidazole derivatives condensed with carbohydrates as a potential antimicrobial agents

The thiazole and imidazole nucleus, as well as carbohydrates are important classes of compounds found in many natural and synthetic products with a wide range of biological activities. Due to the importance of these classes of compounds as antimicrobial agents, the present article reports the synthesis of a new series of nine compounds based on the coupling of 2-mercaptobenzothiazole and 2-mercaptobenzimidazole with different carbohydrates.

Synthesis and antitubercular activity of isoniazid condensed with carbohydrate derivatives

A series of 13 compounds analogous of isoniazid condensed with carbohydrate was synthesized and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv using Alamar Blue susceptibility test and the activity expressed as the minimum inhibitory concentration (MIC90) in μg/mL. Several compounds exhibited antitubercular activity (0.31-3.12 μg/mL) when compared with first line drugs such as isoniazid (INH) and rifampicin (RIP) and could be a good starting point to develop new compounds against tuberculosis.

Synthesis and characterization of n-hydroxyalkyl and oxazolinyl ethionamide derivatives

Multidrug-resistant tuberculosis (MDR-TB) is a serious problem worldwide, especially in people living with human immunodeficiency virus. In considering the MDR-TB problem, ethionamide (ETH) is a structural analog of isoniazid that is typically used when the patient exhibits resistance to the front-line drugs, being one of the most frequently used drugs, for the treatment of drug-resistant tuberculosis. Due to the importance of ETH in TB treatment, the aim of our work was the synthesis and characterization of oxazolinyl (1,2) and N-hydroxyalkyl (3–5) ETH derivatives.

Métodos de preparação e atividade biológica do ácido quinolínico e derivados

In 1981 2,3-pyridine dicarboxylic acid (quinolinic acid) was discovery to be a selective agonist for the N-methyl -D-aspartic acid (NMDA) receptor. As a consequence it possesses neurotoxic activity resulting from overstimulation of the receptor. Quinolinic acid is implicated as an etiological factor in a range of neurodegenerative disease including AIDS related dementia, Huntington´s disease and Lyme disease. In the design of novel therapies to treat these diseases, some molecules have been identified as an important target. In this paper we described different methods to prepare quinolinic acid and derivatives.

High Anti-Inflammatory Activity and Low Toxicity of Thalidomide Analogs

Thalidomide is an immunomodulatoryagent with anti-inflammatory activity, however it may also cause serious side effects. New compounds derived from thalidomide effective in modulating inflammatory responses and having an improved safety profile is being investigated. In this study, two thalidomide analogs, GI-16 and SC-15, were evaluated using the carrageenan-induced paw swelling and the lipopolysaccharide (LPS)-induced lung inflammation in mice. Acute and sub-chronic toxicity of the compounds were investigated in blood and serum samples of Wistar rats by measurements of hematological and biochemical parameters. Histopathological analyses were conducted to assess inflammatory cell infiltration in heart, liver and kidneys. Our results show that treatment with GI-16 and SC-15 reduced the carrageenan-induced paw edema over a 24 hour period. GI-16 and SC-15 treatments inhibited LPS-induced TNF-α and IL-6 in lung homogenates. In contrast, thalidomide and SC-15 enhanced IL-10 (p<0.05). Histopathological analysis showed reduction in LPS–induced lung inflammation after treatment with GI-16 and SC-15. Wistar rats treated with the compounds did not develop any clinical signs of acute or sub-chronic toxicity. No mortality occurred in both control and treated animals and body weight gain over time was similar in all groups. In addition, no significant alterations were detected in enzyme activity of aspartate aminotransferase, alanine aminotransferase or alkaline phosphatase, and no significant alterations were found in glucose, urea, creatinine, total cholesterol or triglyceride levels. GI-16 and SC-15 treatments did not modify hemoglobin, red and white blood cell count, and sections of liver, kidneys and heart tissues showed no pathological alterations under light microscopy. In conclusion, the remarkable in vivo anti-inflammatory activity and low toxicity of SC-15 and GI-16 makes them promising drug candidates to treat inflammatory conditions.

Synthesis of an advanced intermediate of alfa-alloenduracididine from allylglycine

α-Alloenduracididine, 3-(2-amino-4,5-dihydro-1Himidazole-4-yl)-2-aminopropionic acid) 1 and its diastereoisomer, enduracididine 2, are two nonproteinogenic amino acids isolated in 1968 from Streptomyces fungicidicus as part of a cyclopeptide the enduracidine, which has antibiotic activity. 1,2 α-Alloenduracididine, which can be viewed as a constrained analogue of arginine, 3 belongs to a family of natural amino acids having the terminal guanidine nitrogen atom linked to the methylene backbone. Most of these amino acids are components of peptide antibiotics isolated from extracts of microorganisms and include: β-hydroxyenduracididine and β-hydroxyalloenduracididine (constituents of (α-e)-mannopeptimycins), 3 tetrahydrolathyrine, capreomycidine (constituent of capreomycins). Our laboratory has recently completed the first total synthesis and determination the absolute configuration of tetrahydrolathyrine. 4 Here, we described an efficient synthetic route to acess the α-alloenduracididine by synthesis of an advanced intermediate amino alcohol 11 , obtained as diastereoisomers mixture (11a and 11b). Amino alcohol intermediate was synthesized, in eight steps, from ethyl (R)-N-Boc-allylglycinate 4 in satisfactory yields from 4 . Studies concerning the oxidation of the amino alcohol to the amino acid and determination of the absolute configuration at C4 of each diastereoisomer are in progress.