Alexandre José da Silva Góes

Synthesis and evaluation of anti-Toxoplasma gondii and antimicrobial activities of thiosemicarbazides, 4-thiazolidinones and 1,3,4-thiadiazoles

In this work we reported the synthesis and evaluation of anti-Toxoplasma gondii and antimicrobial activities in vitro of three new compound series obtained from ethyl(5-methyl-1-H-imidazole-4-carboxylate): acylthiosemicarbazide analogues 3a-d, 4-thiazolidinone analogues 4a-d and 1,3,4-thiadiazole analogues 5a-d. All synthesized compounds were characterized by IR, (1)H, (13)C NMR and HRMS. The majority of the tested compounds show excellent anti-T. gondii activity when compared to hydroxyurea and sulfadiazine. In addition it was also shown that most of the compounds in this study have a better performance against intracellular tachyzoites. The results for antimicrobial activity evaluation showed weak antibacterial and antifungal activities for all the tested molecules, when compared with the standard drugs (chloramphenicol and rifampicin for antibacterial activity; nistatin and ketoconazole for antifungal activity).

Tiossemicarbazonas: métodos de obtenção, aplicações sintéticas e importância biológica

Thiosemicarbazones are a class of compounds known by their chemical and biological properties, such as antitumor, antibacterial, antiviral and antiprotozoal activity. Their ability to form chelates with metals has great importance in their biological activities. Their synthesis is very simple, versatile and clean, usually giving high yields. They are largely employed as intermediates, in the synthesis of others compounds. This article is a survey of some of these characteristics showing their great importance to organic and medicinal chemistry.Thiosemicarbazones are a class of compounds known by their chemical and biological properties, such as antitumor, antibacterial, antiviral and antiprotozoal activity. Their ability to form chelates with metals has great importance in their biological activities. Their synthesis is very simple, versatile and clean, usually giving high yields. They are largely employed as intermediates, in the synthesis of others compounds. This article is a survey of some of these characteristics showing their great importance to organic and medicinal chemistry.

β-Lapachone: A naphthoquinone with promising antischistosomal properties in mice

The activity of β-lapachone (3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b]pyran-5,6-dione, β-lap) against different stages of Schistosoma mansoni was investigated in mice. Mice infected with 50 cercariae (BH strain) were intraperitoneally treated at a dose of 50 mg/kg for 5 consecutive days, starting on the 1st, 14th, 28th and 45th days after infection, to evaluate the effect of β-lap on skin schistosomula, lung schistosomula, young worms (before oviposition) and adult worms (after oviposition), respectively. All animals were euthanized 60 days after infection. β-Lap significantly reduced (p<0.001) the number of worms in 29.78%, 37.2%, 24.2% and 40.22% when administered during the phases of skin schistosomula, lung schistosomula, young worms and adult worms, respectively. Significant reduction was also achieved in terms of female burden. In all groups, there was significant reduction in the number of eggs and granulomas in the hepatic tissue. When the intervention was performed during the phase of adult worms, β-lap reduced the size of hepatic granulomas and changed the oogram pattern, lowering the percentage of immature eggs and increasing the percentage of mature and dead eggs. Our data indicate that β-lap has moderate antischistosomal properties. Its molecule may also be used as a prototype for synthesis of new naphthoquinone derivatives with potential schistosomicidal properties. Further studies with different formulations containing β-lap are needed to clearly establish the best dose and route of administration and its mechanism of action against schistosomes.

Effect of Semisolid Formulation of Persea Americana Mill (Avocado) Oil on Wound Healing in Rats

The aim of this study was to evaluate the wound-healing activity of a semisolid formulation of avocado oil, SSFAO 50%, or avocado oil in natura, on incisional and excisional cutaneous wound models in Wistar rats. An additional objective was to quantify the fatty acids present in avocado oil. On the 14th day, a significant increase was observed in percentage wound contraction and reepithelialization in the groups treated with 50% SSFAO or avocado oil compared to the petroleum jelly control. Anti-inflammatory activity, increase in density of collagen, and tensile strength were observed inSSFAO 50% or avocado oil groups, when compared to control groups. The analysis of the components of avocado oil by gas chromatography detected the majority presence of oleic fatty acid (47.20%), followed by palmitic (23.66%), linoleic (13.46%) docosadienoic (8.88%), palmitoleic (3.58%), linolenic (1.60%), eicosenoic (1.29%), and myristic acids (0.33%). Our results show that avocado oil is a rich source of oleic acid and contains essential fatty acids. When used in natura or in pharmaceutical formulations for topical use, avocado oil can promote increased collagen synthesis and decreased numbers of inflammatory cells during the wound-healing process and may thus be considered a new option for treating skin wounds.

Anti-parasitic action and elimination of intracellular Toxoplasma gondii in the presence of novel thiosemicarbazone and its 4-thiazolidinone derivatives

Toxoplasma, which infects all eukaryotic cells, is considered to be a good system for the study of drug action and of the behavior of infected host cells. In the present study, we asked if thiosemicarbazone derivatives can be effective against tachyzoites and which morphological and ultrastructural features of host cells and parasites are associated with the destruction of Toxoplasma. The compounds were tested in infected Vero cell culture using concentration screens (0.1 to 20 mM). The final concentration of 1 mM was chosen for biological assay. The following results were obtained: 1) These new derivatives decreased T. gondii infection with an in vitro parasite IC50% of 0.2-0.7 mM, without a significant effect on host cells and the more efficient compounds were 2, 3 (thiosemicarbazone derivatives) and 4 (thiazolidinone derivative); 2) The main feature observed during parasite elimination was continuous morphological disorganization of the tachyzoite secretory system, progressive organelle vesiculation, and then complete disruption; 3) Ultrastructural assays also revealed that progressive vesiculation in the cytoplasm of treated parasites did not occur in the host cell; 4) Vesiculation inside the parasite resulted in death, but this feature occurred asynchronously in different intracellular tachyzoites; 5) The death and elimination of T. gondii was associated with features such as apoptosis-like stage, acidification and digestion of parasites into parasitophorous vacuoles. Our results suggest that these new chemical compounds are promising for the elimination of intracellular parasites by mainly affecting tachyzoite development at 1 mM concentration for 24 h of treatment.

Effect of a Semisolid Formulation of Linum usitatissimum L. (Linseed) Oil on the Repair of Skin Wounds

The purpose of this study was to investigate the effects of a semisolid formulation of linseed oil, SSFLO (1%, 5%, or 10%) or in natura linseed oil on skin wounds of rats. We used wound models, incisional and excisional, to evaluate, respectively, the contraction/reepithelialization of the wound and resistance to mechanical traction. The groups (n = 6) treated with SSFLO (1% or 5%) began the process of reepithelialization, to a significant extent (P < .05), on the sixth day, when compared to the petroleum jelly control group. On 14th day for the groups treated with SSFLO (1% or 5%), 100% reepithelialization was found, while in the petroleum jelly control group, this was only 33.33%. Our study showed that topical administration of SSFLO (1% or 5%) in excisional wounds allowed reepithelialization in 100% of treated animals. Therefore, a therapeutic potential of linseed oil, when used at low concentrations in the solid pharmaceutical formulations, is suggested for the process of dermal repair.

Ultrastructural analysis of β-lapachone-induced surface membrane damage in male adult Schistosoma mansoni BH strain worms.

The present study provides, for the first time, conclusions on the in vitro schistosomicidal properties of β-lap. Adult male Schistosoma mansoni worms of the BH strain were used for the study. Motility, mortality, cell viability and alterations in the tegument were employed as schistosomicidal parameters. Alterations in motility were observed 6h after incubation in concentrations of 50 and 100 μM. β-lap decreased significantly the worm viability, reducing the formation of formazan in 17.7%, 27.4% and 54.8% at concentrations of 25, 50 and 100 μM, respectively. Mortality in concentrations of 50 and 100 μM was of 67% and 100%, respectively, after 24h. The death of the parasite was preceded by progressive surface membrane damage, characterized by tegument peeling, spine reduction and erosion, blister formation and rupture, and the emergence of holes. In addition to this, in the anterior portion, intense general edema, areas of cracking with a wrinkled surface, furrows and a fibrous appearance were also observed. The results of the present study thus provide a sound basis for further in-depth studies of the schistosomicidal properties of β-lap, both in the laboratory and in the field.

Síntese e avaliação da atividade antimicrobiana de novas 4-tiazolidinonas obtidas a partir de formilpiridina tiossemicarbazonas

Twelve novel 4-thiazolidinone derivatives (2a-l) have been synthesized by reacting formilpyridine thiosemicarbazones (1a-l) and anhydride maleic in toluene. Their chemical structures were confirmed by IR, 1H and 13C NMR. The new compounds were submitted to in vitro evaluation against pathogenic Gram-positive, Gram-negative bacteria and yeasts. The findings obtained showed that the compounds 2a, 2d, 2e and 2g were effective against some of the bacterial strains used, whereas the compounds 2d, 2e and 2i exhibited a moderate antifungal activity against the yeast strains evaluated. An initial structure activity relationship (SAR) was established.

Métodos de obtenção, reatividade e importância biológica de 4-tiazolidinonas

Molecules containing the 4-thiazolidinone ring are known to possess a wide range of biological properties including antimicrobial and anti-inflammatory activities among others. These compounds can be synthesized by cyclization reactions involving a-haloacetic acid or a-mercaptoacetic acid and employed in several chemoselective reactions. Comprehensive reviews have been written on 4-thiazolidinones in 1961 by Brown and in 1980 by Singh et al. In the recent literature, some new synthesis methods for 4-thiazolidinone derivatives and several reactions have been reported. These advances warrant to review the chemical and biological properties of compounds with this important heterocycle employed in synthetic organic chemistry and medicinal chemistry.

Mass Spectrometry of Some Benzylidene Imidazolidinediones and Thiazolidinediones. III- Positive and Negative Electron Impact Mass Spectra of Chlorobenzyl Imidazolidinedione or Thiazolidinedione Compounds

Abstract In the present investigation, a study of the electron-impact mass spectrometry in positive- and negative-ion modes is reported for a series of 3-chlorobenzyl-5-benzylidene-imidazolidine-2,4-dione and -thiazolidine-2,4-dione derivatives previously synthetized.