Acaricidal activity of synthetic spilanthol derivative against ticks of medical and veterinary importance.

The ANESPSAT, a synthetic spilanthol derivative, and its nanoformulation were evaluated against Rhipicephalus microplus and Amblyomma sculptum ticks. ANESPSAT activity was compared with spilanthol and derivatives (ANESPE and others). The compound was synthesized in a gram-scale by a 2-step process, comprising a direct ester amidation and a Horner-Wadsworth- Emmons reaction. The nanoemulsions were produced by coarse homogenization followed by high-energy ultrasonication, in which hydrodynamic diameter, polydispersity index, and zeta potential remained stable. The spilanthol-eugenol hybrid derivatives did not show significant acaricidal activity. ANESPE killed 83% of the R. microplus larvae at 30 mg.mL-1, while ANESPSAT killed 97% at 0.5 mg.mL-1, showing to be the most active compound. Spilanthol and ANESPSAT had similar high mortality rates for tick larvae, with LC50 values of 0.10 and 0.14 mg.mL-1 for R. microplus larvae, and 0.04 and 0.48 mg.mL-1 for A. sculptum larvae, respectively. The efficacy of spilanthol was lower against R. microplus engorged females when compared with ANESPSAT, which was highly effective (>98%) against R. microplus engorged females. The nanoemulsion with ANESPSAT was effective against tick females, preventing egg laying and achieving 100% efficacy at 2.5 mg.mL-1. Spilanthol had only 59% efficacy at 10 mg.mL-1. The results suggest that ANESPSAT, a natural product derivative, could be used in novel formulations for tick management that might be safer and environmentally friendly.

In vitro and in silico evidences about the inhibition of MepA efflux pump by coumarin derivatives.

The discovery of antibiotics has significantly transformed the outcomes of bacterial infections in the last decades. However, the development of antibiotic resistance mechanisms has allowed an increasing number of bacterial strains to overcome the action of antibiotics, decreasing their effectiveness against infections they were developed to treat. This study aimed to evaluate the antibacterial activity of synthetic coumarins Staphylococcus aureus in vitro and analyze their interaction with the MepA efflux pump in silico. The Minimum Inhibitory Concentration (MIC) determination showed that none of the test compounds have antibacterial activity. However, all coumarin derivatives decreased the MIC of the standard efflux inhibitor ethidium bromide, indicating antibacterial synergism. On the other hand, the C14 derivative potentiated the antibacterial activity of ciprofloxacin against the resistant strain. In silico analysis showed that C9, C11, and C13 coumarins showed the most favorable interaction with the MepA efflux pump. Nevertheless, due to the present in silico and in vitro investigation limitations, further experimental research is required to confirm the therapeutic potential of these compounds in vivo.

Photobiological effect of eugenol-derived 3-benzoylcoumarin associated with led lights against MDR microorganisms.

The problem of antibiotic resistance by bacteria threatens human health. Therefore, studies in this area seek alternatives to circumvent it. The study with coumarins and eugenol has already proven that these classes of compounds act against bacteria. In this same aspect, exposure to LED also shows a bactericidal effect. Seeking a possible enhancement of this effect, the present work studied coumarins derived from eugenol in association with LED to investigate the bactericidal effect. Four compounds were tested. For this, minimum inhibitory concentrations (MICs) and modulation with three antibiotics against Escherichia coli and Staphylococcus aureus bacteria were determined. To test the behavior of the activity against exposure to LED, the plates were exposed for 20 min to blue light, 415 nm and then incubated at 37°C for 24 h. For control, duplicates were made, and one of them did not undergo this exposure. C1 exhibited better activity against S. aureus, as synergism prevailed under the conditions tested. C3 and C4 were promising against E. coli as they showed synergism in association with the three antibiotics both with and without LED exposure. Thus, the compounds showed bactericidal activity, and LED was shown to enhance synergism.

Allelochemical Activity of Eugenol-Derived Coumarins on Lactuca sativa L.

Coumarins are widely distributed substances in plant species that promote phytotoxic effects, allowing them to be exploited as herbicides less harmful to the environment, since many invasive species have demonstrated resistance to commercially available products. The derived coumarins used in this study had not been tested in plant models and their effect on plants was unknown. The objective of this study was to evaluate the phytotoxic action of these coumarins in bioassays with Lactuca sativa L., in order to select the most responsive substance whose toxicity was best elucidated by chromosomal complement and enzymatic antioxidant metabolism studies. From the phytotoxicity assays, coumarin 8-methoxy-2-oxo-6-(prop-2-en-1-yl)-2H-chromene-3-carboxylic acid (A1), reported here for the first time, was selected as the most responsive and caused a reduction in the following parameters: number of normal seedlings, fresh biomass, root length and shoot length. Subsequent studies demonstrated that this coumarin is cytogenotoxic due to damage caused to the cell cycle and the occurrence of chromosomal abnormalities. However, it did not interfere with antioxidant enzyme activity and did not cause lipid peroxidation. The changes caused by coumarin A1 described herein can contribute to better understanding the allelochemical actions of coumarins and the potential use of these substances in the production of natural herbicides.

In vitro and in vivo trypanocidal activities of 8-methoxy-3-(4-nitrobenzoyl)-6-propyl-2H-cromen-2-one, a new synthetic coumarin of low cytotoxicity against mammalian cells.

Natural and synthetic coumarins have been described as prototypes of new drug candidates against Chagas' disease. During a typical screening with new compounds, we observed the potential of a new synthetic nitrobenzoylcoumarin (1) as trypanocidal against Trypanosoma cruzi epimastigotas. Then, we decided to prepare and evaluate a set of analogues from 1 to check the major structural requirements for trypanocidal activity. The structural variations were conducted in six different sites on the original compound and the best derivative (3) presented activity (IC50 28 ± 3 µM) similar to that of benznidazole (IC50 25 ± 10 µM). The enhancement of trypanocidal activity was conditioned to a change in the side chain at C6 (allyl to n-propyl group) and the preservation of coumarin nucleus and the nitrobenzoyl group at C3. Exposure of 3 to H9C2 cells showed low toxicity (CC50  > 200 µM) and its activity on T. cruzi amastigotes (IC50 13 ± 0.3 µM) encouraged us to perform an evaluation of its potential when given orally to mice infected with trypomastigote forms. Derivative 3 was able to reduce parasitemia when compared to the group of untreated animals. Taken together, these results show the potential therapeutic application of the synthetic coumarins.