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.

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.

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.

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.

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.