In vitro and in silico antibacterial evaluation of coumarin derivatives against MDR strains of Staphylococcus aureus and Escherichia coli.

The increase in antibiotic resistance rates has attracted the interest of researchers for antibacterial compounds capable of potentiating the activity of conventional antibiotics. Coumarin derivatives have been reported to develop effective antibacterials with possible new mechanisms of action for treating infectious diseases caused by bacteria with a profile of drug resistance. In this context, the aim of the present study we have now prepared one variety of new synthetic coumarins evaluating the pharmacokinetic and chemical similarity in silico, their antimicrobial activity against Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922), and potential for the modulation of antibiotic resistance against Staphylococcus aureus (SA10) and Escherichia coli (EC06) clinical isolate bacteria by in vitro assay. The antibacterial activity and antibiotic-enhancing properties were evaluated by the broth microdilution method and pharmacokinetically characterized according to the Lipinsk rule of 5 and had their similarity analyzed in databases such as ChemBL and CAS SciFinder. The results demonstrated that only compound C13 showed significant antibacterial activity (MIC ≤256 µg/mL), and all other coumarins did not display relevant antibacterial activity (MIC ≥1024 µg/mL). However, they did modulate the antibiotics activities to norfloxacin and gentamicin, except, compound C11 to norfloxacin against Staphylococcus aureus (SA10). The in silico properties prediction and drug-likeness results demonstrated that all coumarins presented a good drug-likeness score with no violations and promising in silico pharmacokinetic profiles showing that they have the potential to be developed into an oral drug. The results indicate that the coumarin derivatives showed good in vitro antibacterial activity. These new coumarin derivatives also demonstrated the capacity to modulate antibiotic resistance with potential synergy action for current antimicrobials assayed, as antibiotic adjuvants, to reduce the emergence of antimicrobial resistance.

Botanical sources and heavy metals contents of honey produced by Apis mellifera in an ecotone region of the state of Bahia, Brazil.

The present study investigated by palynological and chemical analysis (Flame Atomic Absortion Spectrometry) about the botanical origin and the heavy metals content (arsenic, cadmium, chromium, lead and mercury) of monthly honey samples of Apis mellifera L. over two years. The pollen types Apiaceae, Mimosa caesalpiniifolia, M. tenuiflora and Myrcia indicated the main floristic sources used by bees. M. tenuiflora was the most frequent of the pollen types, and because it predominates in different months in each year, which may indicate more than one species of the genus being foraged by the beehive. The climatic influence (rainfall and temperature) on the pollen diversity was investigated and was not statistically supported. The chemical analysis showed that the heavy metal content of the samples were below their respective limits of quantification, and, therefore, the samples can be considered safe for human consumption.

Multi-element composition, physicochemical and pollen attributes of honeys from the Paraguaçu River (Bahia, Brazil) by inductively coupled plasma-optical emission spectrometry (ICP OES).

Honey is a food of nutritional, medicinal and commercial importance. The physicochemical characteristics, pollen spectrum and mineral composition of eighteen honey samples obtained from regions (Cachoeira, Coqueiros, Maragojipe and Santiago do Iguape) near the Paraguaçu River, Bahia, Brazil were evaluated. Botanical families Asteraceae, Leguminosae, Malvaceae, Myrtaceae and Palmae were most frequently found. Five samples had water contents above the maximum limit established by the Brazilian legislation (> 20%). The mineral composition was determined by ICP OES, after microwave digestion. Ca, K, Mg and Na were measured (mg Kg-1) in the range from: 18.85 to 79.61; 366.74 to 1214.98; 12.46 to 44.59 and 11.56 to 85.39, respectively. Cu, Fe, Mn and Zn had variable concentration ranges, between 0.05 and 6.13 mg Kg-1. Al, Ba, Cd, Co, Cr, Ni, Pb, Se and V showed values below the LOD. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) demonstrated that there are no similarities of mineral composition among honey samples.

Potentiation of antibiotic activity of aminoglycosides by natural products from Cordia verbenacea DC.

Medicinal plants are often the only therapeutic resource for many communities and ethnic groups. Cordia verbenacea DC., "Erva-baleeira," is one of the species of plants currently used to produce a phytotherapeutic product extracted from its leaves. The present study aimed to establish its chemical profile, antibacterial activity and resistance-modulating potential. The C. verbenacea extracts were prepared from fresh leaves using solvents as methanol and hexane. Ethyl Acetate was used for the preparation of the fraction. Phytochemical screening was carried out using HPLC-DAD for determination and quantification of the secondary metabolites present in the fractions. Antibacterial and resistance-modulation assays were performed to determine minimum inhibitory concentration (MIC) using a microdilution assay. The data were subjected to statistical analysis with two-way ANOVA and Bonferroni posttests. Results of phytochemical prospecting and HPLC analysis of the fractions were in agreement with the literature. The natural products presented moderate antibacterial activity when considering the clinical relevance of a MIC of 256 µg/mL against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, and 512 µg/mL against P. aeruginosa. However, when the fractions were combined with antibiotics we observed a synergic effect, as natural products enhanced the antibacterial effect of aminoglycosides, significantly decreasing the MIC of antibiotics at 12.5%-98.4%. We believe that the data obtained from phytochemical analysis and from antibacterial and resistance modulation assays of C. verbenacea extracts new can open perspectives in the search for new alternatives for the treatment of bacterial infections and stimulate the renewed use of antibiotics with reduced effectiveness due to resistance.

Pollen types and levels of total phenolic compounds in propolis produced by Apis mellifera L. (Apidae) in an area of the Semiarid Region of Bahia, Brazil.

Twenty-two propolis samples produced by Apis mellifera L. in an area of the Semiarid region the the State of Bahia (Agreste of Alagoinhas), Brazil, were palynologically analyzed and quantified regarding their levels of total phenolic compounds. These samples were processed using the acetolysis technique with the changes suggested for use with propolis. We found 59 pollen types belonging to 19 families and 36 genera. The family Fabaceae was the most representative in this study with nine pollen types, followed by the family Asteraceae with seven types. The types Mikania and Mimosa pudica occurred in all samples analyzed. The types Mimosa pudica and Eucalyptus had frequency of occurrence above 50% in at least one sample. The highest similarity index (c. 72%) occurred between the samples ER1 and ER2, belonging to the municipality of Entre Rios. Samples from the municipality of Inhambupe displayed the highest (36.78±1.52 mg/g EqAG) and lowest (7.68 ± 2.58 mg/g EqAG) levels of total phenolic compounds. Through the Spearman Correlation Coefficient we noticed that there was a negative linear correlation between the types Mimosa pudica (rs = -0.0419) and Eucalyptus (rs = -0.7090) with the profile of the levels of total phenolic compounds of the samples.

Evaluation of the Antimicrobial Activity of the Decoction of Tropidurus hispidus (Spix, 1825) and Tropidurus semitaeniatus (Spix, 1825) Used by the Traditional Medicine.

Tropidurus hispidus and Tropidurus semitaeniatus are two lizard species utilized in traditional medicine in Northeast Brazil. Their medicinal use includes diseases related with bacterial infections such as tonsillitis and pharyngitis. They are used in the form of teas (decoctions) for the treatment of illnesses. In this work, we evaluated the antimicrobial activity of the decoctions of T. hispidus (DTH) and T. semitaeniatus (DTS) against bacterial strains, namely, standard and multiresistant Escherichia coli, Staphylococus aureus, and Pseudomonas aureuginosa, alone and in combination with aminoglycoside antibiotics. The decoctions were prepared using the whole body of the dried lizards, and the filtrate was frozen and lyophilized. When tested alone, the samples did not demonstrate any substantial inhibition of bacterial growth. However, in combination with antibiotics as aminoglycosides, decoctions reduced the minimal inhibitory concentration (MIC) of the assayed antibiotics against multiresistant strains of S. aureus and P. aureuginosa. Chemical prospecting tests revealed the presence of alkaloids in DTS. This is the first study evaluating the medicinal efficacy of T. hispidus and T. semitaeniatus and contributes to the list of new sources of medicines from natural products of animal origin.

Palynological origin, phenolic content, and antioxidant properties of honeybee-collected pollen from Bahia, Brazil.

The aim of this study was to determine the palynological origin, phenolic and flavonoid content, and antioxidant properties of twenty-five samples of bee pollen harvested during a nine-month period (February-November) from the Canavieiras municipality (northeastern Brazil). Of the 25 samples analyzed, only two (February 01 and 02) were heterofloral. The predominant pollens in the samples analyzed during that month were: Cecropia, Eucalyptus, Elaeis, Mimosa pudica, Eupatorium, and Scoparia. Ethyl acetate fractions were analyzed by HPLC-DAD. The flavonoids isoquercetin, myricetin, tricetin, quercetin, luteolin, selagin, kaempferol, and isorhamnetin were detected. The flavonoid present in all 22 samples was isolated and identified as isorhamnetin 3-O-b-neohesperidoside. The total phenolic contents determined using the Folin-Ciocalteu reagent ranged from 41.5 to 213.2 mg GAE/g. Antioxidant activities based on the 1,1-diphenyl-2-picryl hydrazyl (DPPH), 2,2-azinobis 3-ethylbenzothiozoline-6-sulfonic acid (ABTS), and Fe2+ ion chelating activity assays were observed for all extracts, and correlated with the total phenolic content.

Trypanocide, cytotoxic, and antifungal activities of Momordica charantia.

CONTEXT: Chagas disease, caused by Trypanosoma cruzi, is a public health problem. Currently, chemotherapy is the only available treatment for this disease, and the drugs used, nifurtimox and benzonidazol, present high toxicity levels. An alternative for replacing these drugs are natural extracts from Momordica charantia L. (Cucurbitaceae) used in traditional medicine because of their antimicrobial and biological activities. OBJECTIVE: In this study, we evaluated the extract of M. charantia for its antiepimastigote, antifungal, and cytotoxic activities. MATERIALS AND METHODS: An ethanol extract of leaves from M. charantia was prepared. To research in vitro antiepimastigote activity, T. cruzi CL-B5 clone was used. Epimastigotes were inoculated at a concentration of 1 × 10(5) cells/mL in 200 µl tryptose-liver infusion. For the cytotoxicity assay, J774 macrophages were used. The antifungal activity was evaluated by microdilution using strains of Candida albicans, Candida tropicalis, and Candida krusei. RESULTS: The effective concentration capable of killing 50% of parasites (IC(50)) was 46.06 µg/mL. The minimum inhibitory concentration (MIC) was ≤ 1024 µg/mL. Metronidazole showed a potentiation of its antifungal effect when combined with an extract of M. charantia. CONCLUSIONS: Our results indicate that M. charantia could be a source of plant-derived natural products with antiepimastigote and antifungal-modifying activity with moderate toxicity.

Systematic review of antiprotozoal potential of antimicrobial peptides.

Protozoa is a group of microorganisms that cause neglected tropical diseases, such as malaria, Chagas disease, and Leishmaniasis. Due to the growing demand for new therapeutic agents, antimicrobial peptides (AMPs) have gained attention for antiprotozoal action. A systematic literature review described the current scenario of plant and animal AMPs with action antiprotozoal. The terms "antimicrobial peptides", "plant", and "animal" combined with the names of the etiological agents were used in the search. Boolean and Operator were used to connect the terms. The search found 4,825 articles. However, 79 articles were excluded because they were duplicates, and 4,627 were excluded based on title and abstract. Therefore, 119 were evaluated and included here. Of these, the use of antimicrobial peptides of animal origin was predominant. Still, the works with plant peptides focused on the genus Leishmania. Only antimicrobial peptides of animal origin were described for the other genera of protozoa (Toxoplasma spp, Trypanosoma spp, Plasmodium spp). Antimicrobial peptides are an excellent option as a pharmacological tool to fight these infections due to their aggregation and extravasation of cellular content through the formation of pores in the cell membrane of these microorganisms.

Chalcone-based molecules: Experimental and theoretical studies on the two-photon absorption and molecular first hyperpolarizability.

Five chalcone-based molecules denominated by C-3 ((E)-1-(4-methoxyphenyl)-3-phenylprop-2-en-1-one), C-4 ((E)-1,3-bis(4-methoxyphenyl)prop-2-en-1-one), C-5 ((E)-1-(benzo[d][1,3]dioxol-5-yl)-3-(4-methoxyphenyl)prop-2-en-1-one), C-6 ((E)-3-(naphthalen-1-yl)-1-phenylprop-2-en-1-one) and C-7 ((E)-1-(4-methoxyphenyl)-3-(naphthalen-1-yl)prop-2-en-1-one) were synthesized by Claisen-Schmidt reaction in solution of NaOH in water/ethanol 2:1. The aldehydes used were benzaldehyde, anisaldehyde, and ß-naphthaldehyde, while the used ketones were acetophenone, p-methoxyacetophenone, and 3,4-methylenedioxyacetophenone. Z-scan and hyper-Rayleigh scattering techniques were used to study the nonlinear optical properties of these compounds in dichloromethane medium. By using Z-scan technique with femtosecond pulses, two-photon absorption cross-sections (σTPA) were determined, while the first molecular electronic hyperpolarizabilities (ßHRS) were evaluated by the hyper-Rayleigh scattering technique, with picosecond pulses. From the recorded two-photon absorption spectra, it was identified that compound C-7 presented the highest σTPA, regarding the HOMO-LUMO transition, with a value of 40 GM, while C-6 achieved the lowest value for the same transition with 13 GM. Concerning the values of the first molecular hyperpolarizability, compound C-4 presented the highest value, 38 × 10-30 cm4 statvolt-1, while C-3 presented the lowest ßHRS value of about 16 × 10-30 cm4 statvolt-1. Time-dependent density functional theory calculations were used to simulate the one- and two-photon absorption spectra, as well to predict the theoretical value of ßHRS in dichloromethane and vacuum medium.

First molecular electronic hyperpolarizability of series of π-conjugated oxazole dyes in solution: an experimental and theoretical study.

In this work, we report the experimental and theoretical first molecular electronic hyperpolarizability (ß HRS) of eleven π-conjugated oxazoles compounds in toluene medium. The Hyper-Rayleigh Scattering (HRS) technique allowed the determination of the experimental dynamic ß HRS values, by exciting the compounds with a picosecond pulse trains from a Q-switched and mode-locked Nd:YAG laser tuned at 1064 nm. Theoretical predictions based on time-dependent density functional theory level using the Gaussian 09 program package were performed with three different functionals (B3LYP, CAM-B3LYP, and M06-2X), to calculate both static and dynamic theoretical ß HRS values. Good accordance was found between the experimental and theoretical values, in particular for the CAM-B3LYP and M06-2X functionals.

Health technology assessment to improve the medical equipment life cycle management.

Health technology assessment (HTA) is a tool to support decision making that is intended to assist healthcare managers in their strategic decisions. The use of HTA as a tool for clinical engineering is especially relevant in the domain of the medical equipment once it could improve the performance of the medical equipment. It would be done by their systematically evaluation in several aspects, in their life cycle. In Brazil, the Institute of Biomedical Engineering (IEB-UFSC) through the clinical engineering area has been working on the development of methodologies and improvements on HTA for medical equipment. Therefore, this paper presents the effort to create specific methodologies that will improve the dissemination of HTA, focusing on incorporation and utilization phase of the medical equipment life cycle. This will give a better support to the decision makers in the management of the health care system.

Modulation of the antibiotic activity by extracts from Amburana cearensis A. C. Smith and Anadenanthera macrocarpa (Benth.) Brenan.

The aim of this study was to verify the possible interactions between ethanol extracts of Amburana cearensis A. C. Smith and Anadenanthera macrocarpa (Benth.) Brenan, combined with six antimicrobial drugs against multiresistant strains of Staphylococcus aureus and Escherichia coli isolated from humans. The antibacterial activity of the extracts was determined using the minimum inhibitory concentration (MIC). The microdilution assay was performed to verify the interactions between the natural products and the antibiotics using a subinhibitory concentration. The activity of amikacin associated with the extract of Anadenanthera macrocarpa against EC 27 was enhanced, demonstrating an MIC reduction from 128 to 4 µg/mL. Among the ß-lactams, no potentiation on its activity was observed, with exception to the antagonism of the natural products with ampicillin against S. aureus 358.

Modulation of the norfloxacin resistance in Staphylococcus aureus by Croton campestris A. and Ocimum gratissimum L.

INTRODUCTION: Some species of Staphylococcus are often recognized as etiological agents of many animal and human opportunistic infections. This study is the first test of change in resistance of antibiotic activity by Croton campestris A. and Ocimum gratissimum L. against multiresistant strains of Staphylococcus aureus. OBJECTIVE: In this study, the hexane and methanol extract of Croton campestris A. and Ocimum gratissimum L. was tested for antibacterial activity alone and in combination with norfloxacin against the strain SA1199B. MATERIALS AND METHODS: The minimum inhibitory concentration (MIC) and the modulatory effect of extracts was assayed using microtitre assay. RESULTS: By the fact of the MIC observed was not clinically relevant (MIC= 512 to ≥1.024 µg/ml), the antibiotic activity of norfloxacin was enhanced when this antibiotic was combined with sub-inhibitory concentrations of extracts, mainly the hexane extracts. CONCLUSIONS: These results indicate that the assayed extracts present compounds that can be used as a putative efflux pump inhibitor, indicating that Croton campestris A. and Ocimum gratissimum L. can be a source of plant derived products with antibiotic modifier activity.

Decision process model to the health technology incorporation.

This study shows a decision model to the indicators acquisition in hospital medical equipment incorporation, based on three domains: decision making, technology assessment and Health Technology (HT) incorporation. When decision making is concerned, an analysis, synthesis and valuation context are approached, as well as the relation to the ways of making both being reflective or deliberate decision. The technology assessment domain corresponds to the choice and applying of multi-criteria methods in supporting the decision, such as: Analytic Hierarchy Process (AHP), Multi-Attribute Failure Mode Analysis (MAFMA), Elimination and Choice Translating Reality (ELECTRE) among others. On the other hand, the HT incorporation domain, the stages of incorporation of HT, which are divided in planning, proposal production and receiving, installation and management. From all of this, a supporting model to the decision to create indicators within the HT incorporation process, as well as to the HT management was obtained. The modeling of the incorporation process, through architecture of three domains, aids the Clinical Engineering need in managing of the medical hospital technology intending to an adequate usage. With the proposed methodology, one can obtain indicators to assist decision making in the process of HT incorporation.