Síntese de 2-(n-morfolina-1-tiocarbonotiol)acetil)-2-amino-4-metil-(tiazol-2-il)-5-carboxilato de etila como potencial agente antimicrobiano / Synthesis of 2- (n-morpholine-1-thiocarbonotiol) acetyl) -2-amino-4-methil- (thiazol-2-il) -5-ethyl carboxylate as a potential antimicrobial agent

Derivados tiazólicos apresentam um espectro diversificado de atividade biológica, podendo ser destacada a atividade antibacteriana. O presente trabalho reporta a síntese de um potencial antibacteriano inédito derivado do núcleo tiazólico (morfolina-tiocarbonotiol)acetamida. Inicialmente o 2-amino-4-metil-(tiazol-5-il)-carboxilato de etila (3) foi obtido com rendimento de 83 % a partir do tratamento de 3-oxo-butanoato de etila com tioureia. Em seguida a reação deste derivado com cloreto de cloroacetila produziu N-(2-cloroacetil)-2-amino-4-metil-(tiazol-2-il)-5-carboxilato de etila (4) em 70 % de rendimento, o qual após tratamento com sal de ditiocarbamato forneceu o composto inédito (5) com rendimento de 80 %. O produto final foi caracterizado por RMN 1H e massas de alta resolução

Hydroxamic acid derivatives: a promising scaffold for rational compound optimization in Chagas disease.

This work describes the antitrypanocidal activity of two hydroxamic acid derivatives containing o-ethoxy (HAD1) and p-ethoxy (HAD2) as substituent in the aromatic ring linked to the isoxazoline ring. HAD1 and HAD2 induced a significant reduction in the number of intracellular parasites and consequently showed activity on the multiplication of the parasite. Treatment of cardiomyocytes and macrophages with the compounds revealed no significant loss in cell viability. Ultrastructural alterations after treatment of cardiomyocytes or macrophages infected by Trypanosoma cruzi with the IC50 value of HAD1 revealed alterations to amastigotes, showing initial damage seen as swelling of the kinetoplast. This gave a good indication of the ability of the drug to permeate through the host cell membrane as well as its selectivity to the parasite target. Both compounds HAD1 and 2 were able to reduce the cysteine peptidases and decrease the activity of metallopeptidases

Evaluation of 3-(3-chloro-phenyl)-5-(4-pyridyl)-4,5-dihydroisoxazole as a Novel Anti-Inflammatory Drug Candidate

BACKGROUND: 3-(3-chloro-phenyl)-5-(4-pyridyl)-4,5-dihydroisoxazole (DIC) is a five-membered heterocyclic compound containing a N-O bond. The anti-inflammatory effects of this compound were studied both in vitro and in vivo. PRINCIPAL FINDINGS: DIC effectively decreased TNF-α and IL-6 release from LPS-stimulated macrophages in a dose dependent manner. DIC diminished the levels of COX-2 with subsequent inhibition of PGE(2) production. DIC also compromised HMGB1 translocation from the nucleus to the cytoplasm. Moreover, DIC prevented the nuclear translocation of NF-κB and inhibited the MAPK pathway. In vivo, DIC inhibited migration of neutrophils to the peritoneal cavity of mice. CONCLUSIONS: This study presents the potential utilization of a synthetic compound, as a lead for the development of novel anti-inflammatory drugs

Sorption of 2-Chlorophenol from aqueous solutions by functionalized cross-linked polymers

This manuscript describes the synthesis of three polymers based on styrene (STY), divinylbenzene (DVB) and two different vinyl monomers: methyl methacrylate (MMA) and acrylonitrile (AN). The STY-DVB, STY-DVB-MMA and STY-DVB-AN polymers were synthesized employing the aqueous suspension technique. Reaction yields were 73%, 81% and 75%, respectively. They were morphological and chemically characterized using different techniques. The extraction capacity of the polymers was evaluated using 2-chlorophenol. The polymer extraction capacities were evaluated varying contact time the (1 h, 3 h and 5 h), temperature (30 °C, 35 °C and 40 °C), and pH (3, 5.6 and 8). The STY-DVB-AN polymer was the most efficient; it removed around 95% of the analyte using a contact time 50 h

Evaluation of bactericidal action of 2-vinylpiridine copolymers containing quaternary ammonium groups and their charge transfer complexes

We report the development of copolymers based on 2-vinylpyridine with different porosity degrees. The copolymers were quaternized with methyl iodide and acrylonitrile to introduce quaternary ammonium groups on pyridine units. To prepare charge transfer complexes, the unmodified copolymers and their derivatives quaternized were impregnated with iodine. The antibacterial properties of all the polymers were evaluated ranging from of the Escherichia coli strain. The unmodified copolymers did not have antibacterial activity against E.Coli suspensions. The quaternization with methyl iodine and acrylonitrile increased the biocidal performance of these copolymers, but only the copolymer with the lowest porosity modified with methyl iodine showed significant bactericidal action for all E. Coli concentrations. The 2-vinylpiridine copolymers quaternized and impregnated with iodine had higher antibacterial activity than the impregnated ones. The charge transfer complexes derived from the copolymer with the lowest porosity and highest swelling capacity in water had the best bactericidal performance

Preparação de copolímeros à base de 2-vinilpiridina com propriedades bactericidas

We report the development of two copolymers based on 2-vinylpyridine, styrene and divinylbenzene (2Vpy-Sty-DVB) with different porosity degrees. The copolymers were subsequently quaternized with methyl iodide. To prepare charge transfer complexes, the unmodified copolymers and their derivatives quaternized with methyl iodine were impregnated with iodine. The antibacterial properties of the polymers were evaluated in dilutions ranging from 10² to 10(7) cells/mL of the auxotrophic OHd5-K12 Escherichia coli strain. It was possible to obtain materials with complete antibacterial activity even in the highest cell concentrations tested

Chemical structure of 3-(3-chloro-phenyl)-5-(4-pyridyl)-4,5-dihydroisoxazole, DIC.

<p>Chemical structure of 3-(3-chloro-phenyl)-5-(4-pyridyl)-4,5-dihydroisoxazole, DIC.</p

Effect of DIC on nuclear translocation of HMGB1.

<p>RAW 264.7 macrophages were pretreated with DIC 200 µM for 2 h prior to addition of LPS (1 µg/mL) for 24 h. Intracellular HMGB1 was visualized with green immunofluorescent FITC-staining. Untreated cells (UT); LPS-stimulated cells (LPS); DIC-treated cells stimulated with LPS (LPS + DIC).</p

Effect of DIC on macrophage viability.

<p>RAW 264.7 macrophages were treated with DIC (from 10 µM to 500 µM) for 24 h. Cell viabilities were determined by LDH release (<b>A</b>) and MTT assay (<b>B</b>). Values represent means ± SD of three independent experiments. * Significant differences (p>0.05) between treated and untreated cells (250–500 µM), using unpaired t-test.</p

Effect of DIC on LPS-induced TNF-α and IL-6 production.

<p><b>A</b> and <b>B</b>, following pretreatment with Polymyxin B (Pol B, 15 µg/mL), vehicle (DMSO 0.25%) or DIC (10−200 µM) for 2 h, the cells were treated with LPS (100 ng/mL) for 4 h (A) or 24 h (B). Negative control (CTRL −): cell medium only; Positive control (CTRL +): cells stimulated with LPS, only. TNF-α and IL-6 levels were assayed by ELISA. Values represent means ± SD of three independent experiments. NS, non-significant <i>vs</i> CTRL +; * p<0.05 <i>vs</i> vehicle; ** non-significant <i>vs</i> vehicle. Significances between treated groups were determined using unpaired t-test.</p