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.

Investigation of 8-methoxy-3-(4-nitrobenzoyl)-6-propyl-2H-chromen-2-one as a promising coumarin compound for the development of a new and orally effective antileishmanial agent.

Changes in host immunity and parasite resistance to drugs are among the factors that contribute to decreased efficacy of antiparasitic drugs such as the antimonial compounds pentamidine, amphotericin (AMP B) and miltefosine. Bioactive natural products could be alternatives for the development of new drugs to treat neglected human diseases such as leishmaniasis. Natural coumarins and synthetic analogues have shown leishmanicidal activity, mainly in vitro. This study investigated the in vitro and in vivo leishmanicidal activity of synthetic coumarin compounds (C1-C5) in parasites Leishmania (L.) amazonensis and L. (L.) infantum chagasi. The cytotoxicity of these compounds in mammalian cells and their influence on production of reactive oxygen species was also investigated. In vitro assays showed that 8-methoxy-3-(4-nitrobenzoyl)-6-propyl-2H-chromen-2-one (C4) was as active as AMP B mainly in the amastigote form (p < 0.05); C4 presented a selectivity index (65.43) four times higher than C2 (15.4) in L. amazonensis and six times higher (33.94) than C1 (5.46) in L. infantum chagasi. Additionally, coumarin C4 reduced the H2O2 concentration 32.5% more than the control group in L. amazonensis promastigotes during the lag phase of proliferation. No interference of C4 was observed on the mitochondrial membrane potential of the parasites. In vivo, coumarin C4 in corn oil (oral route) led to a reduction in the number of amastigotes from L. infantum chagasi to 1.31 × 106 and 4.09 × 104 in the spleen and liver, respectively (p < 0.05). Thus, C4 represents a candidate for further studies aiming at new treatments of leishmaniasis.