RESUMO
In the past two decades, the increase in microbial resistance to conventional antimicrobials has spurred scientists around the world to search tirelessly for new treatments. Synthetic amino acid-based surfactants constitute a promising alternative to conventional antimicrobial compounds. In this work, two new cationic amino acid-based surfactants were synthesized and their physicochemical, antifungal and antibiofilm properties evaluated. The surfactants were based on phenylalanine-arginine (LPAM) and tryptophan-arginine (LTAM) and prepared from renewable raw materials using a simple chemical procedure. The critical micelle concentrations of the new surfactants were determined by conductivity and fluorescence. Micellization of LPAM and LTAM took place at 1.05 and 0.54 mM, respectively. Both exhibited good antifungal activity against fluconazole-resistant Candida spp. strains, with a low minimum inhibitory concentration (8.2 µg/mL). Their mechanism of action involves alterations in cell membrane permeability and mitochondrial damage, leading to death by apoptosis. Furthermore, when LPAM and LTAM were applied with Amphotericin B, a significant synergistic effect was observed against all the studied Candida strains. These new cationic surfactants are also able to disperse biofilms of Candida spp. at low concentrations. The results indicate that LPAM and LTAM have potential application to combat the advance of fungal resistance as well as microbial biofilms.
Assuntos
Antifúngicos , Fluconazol , Anfotericina B/farmacologia , Antifúngicos/farmacologia , Arginina , Biofilmes , Candida , Farmacorresistência Fúngica , Fluconazol/farmacologia , Testes de Sensibilidade Microbiana , Fenilalanina , Tensoativos/farmacologia , TriptofanoRESUMO
Ketamine is a potent uncompetitive NMDA receptor antagonist that provides amnesia, analgesia, environmental dissociation and immobility, where it has its cytotoxic effect well described in the literature. However, the work on its genotoxic/mutagenic potentials are scarce and insufficient and does not allow a reasonable evaluation of its role. Thus, in the present work, we decided to evaluate the genotoxic and mutagenic effects of ketamine on human peripheral blood leukocytes (PBLs) and Salmonella typhimurium (TA98, TA97a, TA100, and TA102) through several well-established experimental protocols based on different parameters in the presence or not of exogenous metabolizing S9 fraction. Our data revealed that ketamine induces a weak cytotoxic effect on human PBLs after 24â¯h and is devoided of hemolytic effects. A small amount of DNA strand breaks levels were detected in the modified comet assay (employment of FPG enzyme) only at highest concentrations (500 and 700⯵g/mL) of ketamine, highlighting our pro-oxidant data regarding ketamine. However, the oxidative DNA lesions were almost completely repaired which reflects in the lack of mutagenesis (micronuclei and chromosomal aberrations) on human PBLs and no increases in revertants numbers on S. typhimurium/microsome test (500 to 5000⯵g/plate). In summary, ketamine is a weak oxidative DNA damaging agent and is devoid of mutagenic properties on eukaryotic and prokaryotic models.
Assuntos
Anestésicos Dissociativos/toxicidade , Ketamina/toxicidade , Leucócitos/efeitos dos fármacos , Mutagênicos/toxicidade , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Aberrações Cromossômicas/induzido quimicamente , Ensaio Cometa , Quebras de DNA , Dano ao DNA , Hemólise/efeitos dos fármacos , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Testes de Mutagenicidade , Estresse OxidativoRESUMO
Emergence of methicilin resistant Staphylococcus aureus (MRSA) strains is a major cause of infirmity worldwide and has limited our therapeutic options against these pathogens. In this regard, the search for candidates with an antimicrobial activity, with a greater efficacy and a lower toxicity, is necessary. As a result, there is greater need to search for resistance modifying agents which, in combination with existing drugs, will restore the efficacy of these drugs. The antibacterial effect of fluoxetine was determined by a broth microdilution method (the M07-A9 method of the Clinical and Laboratory Standard Institute) and flow cytometry techniques in which the probable mechanism of action of the compound was also assessed. The isolates used in the study belonged to the Laboratory of Bioprospecting of Antimicrobial Molecules (LABIMAN) of the Federal University of Ceará. After 24â¯h, Methicillin-resistant Sthaphylococcus aureus (MRSA) strains showed fluoxetine MICs equal to 64⯵g/mL and 128⯵g/mL, respectively. Cytometric analysis showed that treatment with fluoxetine caused alterations to the integrity of the plasma membranes and DNA damage, which led to cell death, probably by apoptosis.