Marcos Reinaldo da Silva

COLOUR REMOVAL OF DYES FROM SYNTHETIC AND REAL TEXTILE WASTEWATERS IN ONE-AND TWO-STAGE ANAEROBIC SYSTEMS

Decolourisation of the azo dye model compound, Congo Red (CR), and real textile wastewater, was assessed in one- and two-stage anaerobic treatment systems (R₁ and R₂, respectively). High colour removals were achieved in both treatment systems even when a very high CR concentration (1.2 mM) was applied. However, R₂ presented a slightly better stability, in which the acidogenic reactor (R(2,A)) played a major role on dye reduction, as compared to the methanogenic reactor (R(2,M)), evidencing the role of fermentative microorganisms. The minimum electron donor concentration required to sustain dye reduction was much higher than the stoichiometric amount. Additionally, a decrease on the hydraulic retention time (from 24 to 12 h) did not significantly affect decolourisation, indicating that electron transfer was not a concern. Finally, experiments with real textile wastewater showed low decolourisation efficiencies in both systems, most likely due to the presence of dyes not susceptible to reductive decolourisation under these experimental conditions.

Synthesis and Antifungal Activity In Vitro of Isoniazid Derivatives against Histoplasma capsulatum var. capsulatum

ABSTRACT Histoplasmosis is a severe infection that affects millions of patients worldwide and is endemic in the Americas. Amphotericin B (AMB) and itraconazole are highly effective for the treatment of severe and milder forms of the disease, but AMB is toxic, and the bioavailability of itraconazole is erratic. Therefore, it is important to investigate new classes of drugs for histoplasmosis treatment. In this study, a series of nine isoniazid hydrazone derivatives were synthesized and evaluated for their antifungal activities in vitro against the dimorphic fungus Histoplasma capsulatum var. capsulatum. The drugs were tested by microdilution in accordance with CLSI guidelines. The compound N′-(1-phenylethylidene)isonicotinohydrazide had the lowest MIC range of all the compounds for the yeast and filamentous forms of H. capsulatum. The in vitro synergy of this compound with AMB against the planktonic and biofilm forms of H. capsulatum cells was assessed by the checkerboard method. The effects of this hydrazone on cellular ergosterol content and membrane integrity were also investigated. The study showed that the compound alone is able to reduce the ergosterol content of planktonic cells and can alter the membrane permeability of the fungus. Furthermore, the compound alone or in combination with AMB showed inhibitory effects against mature biofilms of H. capsulatum. N′-(1-Phenylethylidene)isonicotinohydrazide alone or combined with AMB might be of interest in the management of histoplasmosis.

Regioselective preparation of thiamphenicol esters through lipase-catalyzed processes

The lipase-catalyzed synthesis of thiamphenicol derivatives has been studied through complementary acylation and hydrolytic approaches, finding Candida antarctica lipase B as the most efficient biocatalyst for the selective modification of both thiamphenicol and thiamphenicol diacetate, respectively. The best results have been obtained using acylation reactions with different vinyl esters of variable length, yielding the corresponding 3-monoesters with excellent yields and in short reaction times. The conditions have been analyzed in terms of substrate concentration, enzyme loading and type of acyl donor. The reuse of the enzyme for five-times without significant loss of the activity has also been demonstrated. Alternatively, the hydrolytic approach has allowed the preparation of some 1-monoesters in good yields, although the reactivity and selectivity levels were lower than the ones achieved for the complementary acetylation reaction.

Synthesis and in vitro antifungal activity of isoniazid-derived hydrazones against Coccidioides posadasii.

Coccidioidomycosis is a potentially severe infection caused by dimorphic fungi Coccidioides immitis and Coccidioides posadasii. Although guidelines are well established, refractory disease is a matter of concern in the clinical management of coccidioidomycosis. In the present study three isoniazid-derived hydrazones N-[(E)-1-(4-methoxyphenyl)ethylidene]pyridine-4-carbohydrazide, N-[(E)-1-(4-methylphenyl)ethylidene]pyridine-4-carbohydrazide, and N-[(E)-1-(phenyl)ethylidene]pyridine-4-carbohydrazide were synthesized and evaluated for antifungal activity against C.xa0posadasii. Susceptibility assays were performed by macrodilution testing. Interactions between the hydrazones and amphotericin B or itraconazole were evaluated by the checkerboard method. We also investigated the impairment of such compounds on cell ergosterol and membrane integrity. The synthesized molecules were able to inhibit C.xa0posadasii inxa0vitro with MIC values that ranged from 25 to 400xa0μg/mL. Drug interactions between synthesized molecules and amphotericin B proved synergistic for the majority of tested isolates; regarding itraconazole, synergism was observed only when strains were tested against N-[(E)-1-(phenyl)ethylidene]pyridine-4-carbohydrazide. Reduction of cellular ergosterol was observed when strains were challenged with the hydrazones alone or combined with antifungals. Only N-[(E)-1-(4-methylphenyl)ethylidene]pyridine-4-carbohydrazide altered membrane permeability of C.xa0posadasii cells. Isoniazid-derived hydrazones were able to inhibit C.xa0posadasii cells causing reduction of ergosterol content and alterations in the permeability of cell membrane. This study confirms the antifungal potential of hydrazones against pathogenic fungi.

The semi-synthetic molecule [4″,5″] dihydro-obovatin isolated from Tephrosia Toxicaria pers reduces zymosan-induced temporomandibular joint inflammatory hypernociception in rats

Arthritis possesses inflammatory components and flavonoids of well-known structures exert anti-inflammatory activity. Here, we aim to evaluate the effects of [4″,5″] dihydro-obovatin and three structurally-defined flavonoids from Tephrosia toxicaria Pers roots on the zymosan-induced temporomandibular joint inflammatory hypernociception in rats as well as their toxicity. Rats were pretreated with the flavonoids (1 and 10u2009mg/kg) and [4″,5″] dihydro-obovatin (0.1 and 1.0u2009mg/kg) 1u2009h before intra-articular zymosan injection (2u2009mg, 40u2009μL). Von Frey test was used to evaluate the nociceptive threshold at the 4th hour after zymosan injection. Six hours after zymosan injection, synovial lavage was collected for total cell counting. Acute toxicity assay for [4″,5″] dihydro-obovatin (1, 10, and 100u2009mg/kg) were performed along with the subchronic toxicity assay by administering [4″,5″] dihydro-obovatin (0.01u2009mg/kg) or saline solution for 14 consecutive days and the rota-rod test was carried out to determine whether [4″,5″] dihydro-obovatin would impair motor functions. The tested flavonoids and [4″,5″] dihydro-obovatin increased nociceptive threshold and reduced the cell counting in the synovial lavage in the temporomandibular joint compared with the zymosan group. [4″,5”] dihydro-obovatin did not induce toxic effects as well as did not alter the motor function in the rota-rod test. The flavonoids and [4″,5″] dihydro-obovatin exerted antinociceptive and anti-inflammatory effects on the zymosan-induced temporomandibular joint inflammatory hypernociception in rats and the latter did not show significant toxic effects. Therefore, [4″,5″] dihydro-obovatin would be a promising anti-inflammatory and antinociceptive agent.

Antinociceptive, anti-inflammatory and toxicological evaluation of semi-synthetic molecules obtained from a benzyl-isothiocyanate isolated from Moringa oleifera Lam. in a temporomandibular joint inflammatory hypernociception model in rats

Inflammation is a key component of many clinical conditions that affect the temporomandibular joint (TMJ) and Moringa oleifera Lam. has been used to treat inflammatory diseases. Here, we evaluated the toxicological effects on mice of a naturally-occurring isothiocyanate from M. oleifera and its seven analogue molecules. Further, the anti-nociceptive and anti-inflammatory effects on a rat model of TMJ inflammatory hypernociception were assessed. The systemic toxicological profile was determined in mice over a 14-day period: MC-1 1u202fμg/kg; MC-D1 1u202fμg/kg, MC-D3 100u202fμg/kg, MC-D6 1u202fμg/kg, MC-D7 1u202fμg/kg, MC-D8 1u202fμg/kg, MC-D9 10u202fμg/kg, and MC-H 1u202fμg/kg. The safest molecules were assayed for anti-nociceptive efficacy in the formalin (1.5%, 50u202fμL) and serotonin (255u202fmg) induced TMJ inflammatory hypernociception tests. The anti-inflammatory effect was evaluated through the vascular permeability assay using Evans blue. Further, the rota-rod test evaluated any motor impairment. Among the tested molecules, MC-D7, MC-D9, and MC-H were not toxic at the survival rate test, biochemical, and hystological analysis. They reduced the formalin-induced TMJ inflammatory hypernociception, but only MC-H decreased the serotonin-induced TMJ inflammation, suggesting an adrenergic receptor-dependent effect. They diminished the plasmatic extravasation, showing anti-inflammatory activity. At the rota-rod test, no difference was observed in comparison with control groups, reinforcing the hypothesis of anti-nociceptive effetc without motor impairment in animals. The analogues MC-D7, MC-D9, and MC-H were safe at the tested doses and efficient in reducing the formalin-induced TMJ hypernociception in rats. Our next steps include determining their mechanisms of anti-nociceptive action.