An overview of New Psychoactive Substances (NPS) in northeast Brazil: NMR-based identification and analysis of ecstasy tablets by GC-MS.

The actual illicit market for synthetic drugs is characterized by a wide variety of psychoactive substances of different chemical and pharmacological classes, such as amphetamine-type stimulants and new psychoactive substances. The knowledge about its chemical composition, as well as the nature and quantity of the active substances present, is important for emergency care in intoxication cases by these substances and to establish adequate chemical and toxicological analysis procedures in forensic laboratories. The aim of this work was to study the prevalence of amphetamine-type stimulants and new psychoactive substances in the states of Bahia and Sergipe, in the northeast region of Brazil, involving samples of drugs seized by the local police forces from 2014 to 2019. In a total of 121 seized and analyzed samples, in which ecstasy tablets predominated (n = 101), nineteen substances were identified using GC-MS and 1D NMR techniques, comprising classical synthetic drugs and new psychoactive substances (NPS). In order to determine the composition of ecstasy tablets, an analytical method based on GC-MS was applied after validation. Analyzes of 101 ecstasy tablets showed that MDMA was the main substance, being found in 57% of the samples, in amounts between 27.3 and 187.1 mg per tablet. In addition, mixtures of MDMA, MDA, synthetic cathinones and caffeine were observed in 34 samples. These results demonstrate that the variety of substances found and the composition of seized materials in northeast Brazil is similar to other studies carried out previously in other Brazilian regions.

Probing human proteins for short encrypted antimicrobial peptides reveals Hs10, a peptide with selective activity for gram-negative bacteria.

BACKGROUND: Some cationic and amphiphilic α-helical segments of proteins adsorb to prokaryotic membranes when synthesized as individual polypeptide sequences, resulting in broad and potent antimicrobial activity. However, amphiphilicity, a determinant physicochemical property for peptide-membrane interactions, can also be observed in some ß-sheets. METHODS: The software Kamal was used to scan the human reference proteome for short (7-11 amino acid residues) cationic and amphiphilic protein segments with the characteristic periodicity of ß-sheets. Some of the uncovered peptides were chemically synthesized, and antimicrobial assays were conducted. Biophysical techniques were used to probe the molecular interaction of one peptide with phospholipid vesicles, lipopolysaccharides (LPS) and the bacterium Escherichia coli. RESULTS: Thousands of compatible segments were found in human proteins, five were synthesized, and three presented antimicrobial activity in the micromolar range. Hs10, a nonapeptide fragment of the Complement C3 protein, could inhibit only the growth of tested Gram-negative microorganisms, presenting also little cytotoxicity to human fibroblasts. Hs10 interacted with LPS while transitioning from an unstructured segment to a ß-sheet and increased the hydrodynamic radius of LPS particles. This peptide also promoted morphological alterations in E. coli cells. CONCLUSIONS: Data presented herein introduce yet another molecular template to probe proteins in search for encrypted membrane-active segments and demonstrates that, using this approach, short peptides with low cytotoxicity and high selectivity to prokaryotic cells might be obtained. GENERAL SIGNIFICANCE: This work widens the biotechnological potential of the human proteome as a source of antimicrobial peptides with application in human health.

Recycling of wastes from fish beneficiation by composting: chemical characteristics of the compost and efficiency of their humic acids in stimulating the growth of lettuce.

Waste from the beneficiation of fish was composted with crushed grass aiming to characterize their chemical composition and investigate the possibility of the use of the final compost as source of humic acids (HA) able to stimulate the growth of lettuce. Compost presented pH value, C/N ratio, and electrical conductivity that allow its use as an organic fertilizer. The element content was present in the following order of abundance in the compost: P > Ca > N > Mg > K > Fe > Zn > Mn > Mo > Cu, and the humus composition was similar to that observed in others kind of organic residues composted. The high content of oxygen pointed out a high level of oxidation of HA, in line with the predominance of phenolic acidity in the functional groups. The 13C-NMR spectra showed marked resonances due to the presence of lipids and other materials resistant to degradation as methoxy substituent and N-alkyl groups. A concentration of 20 mg L-1 HA increased significantly both dry and wet root matter in lettuce but the CO2 assimilation, stomatal conductance, and number of lateral roots of the plants were not affected. However, increases of 64% in the water-use efficiency was observed due to the HA addition, probably related to the root morphology alteration which resulted in 1.6-fold increase of lateral root average length and due to the higher H+ extrusion activity. Reuse of residues from the fish beneficiation activity by composting may represent a safe tool to increase the value of recycled organic residues and generate HA with potential use as plant growth stimulants.

Purified citritin in combination with vancomycin inhibits VRE in vitro and in vivo.

Gram-positive pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) have been frequently associated with bacterial resistance mechanisms. These mechanisms, in turn, restrict a range of therapeutic opportunities for the treatment of infections caused by these micro-organisms. Faced with this problem, the present study aims to isolate and characterize molecules with antimicrobial activity derived from the fungus Penicillium citrinum isolated from Cerrado soil. Furthermore, we also tested possible antibacterial potential alone and in combination with commercial antimicrobial agents. In this context, citrinin was isolated and characterized by nuclear magnetic resonance and electrospray ionization. Functional analyses showed MIC of 128 µg ml-1 against S. aureus ATCC 25923, E. faecalis ATCC 29212 and a clinical isolate of vancomycin-resistant E. faecium (VRE01). However, for a clinical strain of methicillin-resistant S. aureus (MRSA01), the MIC was 256 µg ml-1. In order to avoid such high concentrations and reduce the collateral effects, additive effects were evidenced by combining citrinin with cefoxitin against MRSA01 (FIC index=0.5) and also citrinin with vancomycin toward VRE01 (FIC index=0.5). In vivo studies with BALB/c-tipe mice (MRSA assay) demonstrated a clinical ineffectiveness of cefoxitin associated with citrinin (9.8 mg kg-1 of cefoxitin +0.2 mg kg-1 of citrinin), with this combination being inefficient to increase animal survival. However, the combination used in the treatment of VRE (23.5 mg kg-1 of citrinin +1.5 mg kg-1 of vancomycin) sepsis model was extremely promising, leading to an animal survival rate of 80 percent. In summary, our data show, for the first time, the possible successful use of citrinin associated with vancomycin for pathogenic bacteria control.

Phosphatase activity and its relationship with physical and chemical parameters during vermicomposting of filter cake and cattle manure.

BACKGROUND: Recycling of phosphorus (P) from organic residues (ORs) is important to develop environmentally friendly agriculture. The use of this P source depends on phosphatase enzymes, which can be affected by a chain of parameters during maturation of ORs. In this study the phosphatase activity levels throughout vermicomposting of filter cake (FC) and cattle manure (CM) were correlated with different physical and chemical parameters in an effort to increase the knowledge about recycling of P from ORs. RESULTS: FC presented higher total nitrogen content (TNC), total organic carbon (TOC), humic acid (HA) content, water-soluble P (WSP), phosphatase activities and nanopore volume than CM during vermicomposting. Decreases in TOC of CM resulted from carbohydrate mineralization, which was not observed for FC. CM showed increased hydrophobic index during vermicomposting while FC showed a slight decrease. CONCLUSION: Phosphatase activities correlated positively with TOC, pH and WSP and negatively with HA content for both vermicomposts. Nanopore volume was negatively correlated with phosphatase activities for FC but not for CM. No correlations between hydrophobicity and phosphatase activities were found for FC. Increased hydrophobicity throughout vermicomposting of CM could be partially associated with decreases in phosphatase levels.

Anti-leukemia activity of semi-synthetic phenolic derivatives from Polygonum limbatum Meisn.

BACKGROUND: The present report describes the semi-synthesis of a few O-prenylated phenolic derivatives and their in vitro antitumor activities. These compounds were prepared by modifying two naturally occurring antitumor phenols, 5,7-dihydroxy-3-(1'-hydroxy-1'-phenyl-methyl)-6-methoxy-chroman-4-one (A) and 2',4'-dihydroxy-3',6'-dimethoxychalcone (B), previously isolated from Polygonum limbatum Meisn. (Polygonaceae). The structures were elucidated by spectroscopic means and comparison with published data. The cytotoxicity of compounds was determined by using the resazurin assay in the parental drug-sensitive CCRF-CEM cell line and its multidrug-resistant P-glycoprotein-over-expressing subline, CEM/ADR5000. RESULTS: We describe in the present paper four new semi-synthetic derivatives of A and B: 5-hydroxy-6-methoxy-7-O-(3'-methylbut-2'-enyl)chroman-4-one (1), trivially named metapchromone, 5-acetoxy-6-methoxy-7-O-[3'-methylbut-2'enyl]chroman-4-one (2), trivially named sargisin, 2'-hydroxy-3',6'-dimethoxy-4'-O-(3″-methylbut-2″-enyl)chalcone (3) trivially named limbachalcone A, and 2'-acetoxy-3',6'-dimethoxy-4'-O-(3″-methylbut-2″-enyl)chalcone (4) trivially named tsedengchalcone. Their preliminary cytotoxic activities have been determined. We also report herein the isolation of 1-methylhydantoin (C) and betulinic acid (D) from Polygonum limbatum for the first time. CONCLUSIONS: The study clearly suggests that semi-synthesis involving O-prenylation and acetylation of chalcones or other chromanones should be avoided in a search for anticancer drugs. This conclusion should be helpful when selecting substituents for the synthesis of potential anticancer drugs.

Complete assignment of NMR data of 22 phenyl-1H-pyrazoles' derivatives.

Complete assignment of (1)H and (13)C NMR chemical shifts and J((1)H/(1)H and (1)H/(19)F) coupling constants for 22 1-phenyl-1H-pyrazoles' derivates were performed using the concerted application of (1)H 1D and (1)H, (13)C 2D gs-HSQC and gs-HMBC experiments. All 1-phenyl-1H-pyrazoles' derivatives were synthesized as described by Finar and co-workers. The formylated 1-phenyl-1H-pyrazoles' derivatives were performed under Duff's conditions.

Enterocolite neutropênica: relato de caso / Neutropenic enterocolitis: case report

Enterocolite neutropênica, enterocolite necrotizante ou tiflite compreende um processo necrotizante que envolve principalmente o ceco na presença de neutropenia. Geralmente, ocorre em associaçäo com episódios prolongados de granulocitopenia ou uso prolongado de antibióticos de largo espectro em pacientes com leucemia aguda, embora qualquer paciente neutropênico apresente risco de desenvolvê-la. Relatamos o caso de uma paciente de 19 anos, com leucemia mielóide aguda, que, ao receber drogas quimioterápicas, evoluiu com piora do estado geral, dor, distensäo abdominal e diarréia. A hipótese de tiflite foi confirmada por meio de exames de imagem e antibioticoterapia adequada foi instituída prontamente. A paciente faleceu duas semanas após o diagnóstico, decorrente de outras complicaçöes clínicas, apesar da resoluçäo clínica da tiflite.