The newly synthesized thiazole derivatives as potential antifungal compounds against Candida albicans.
Anna BiernasiukAnna Berecka-RycerzAnna GumieniczekMaria MalmKrzysztof Z ŁączkowskiJolanta SzymańskaAnna MalmPublished in: Applied microbiology and biotechnology (2021)
Recently, the occurrence of candidiasis has increased dramatically, especially in immunocompromised patients. Additionally, their treatment is often ineffective due to the resistance of yeasts to antimycotics. Therefore, there is a need to search for new antifungals. A series of nine newly synthesized thiazole derivatives containing the cyclopropane system, showing promising activity against Candida spp., has been further investigated. We decided to verify their antifungal activity towards clinical Candida albicans isolated from the oral cavity of patients with hematological malignancies and investigate the mode of action on fungal cell, the effect of combination with the selected antimycotics, toxicity to erythrocytes, and lipophilicity. These studies were performed by the broth microdilution method, test with sorbitol and ergosterol, checkerboard technique, erythrocyte lysis assay, and reversed phase thin-layer chromatography, respectively. All derivatives showed very strong activity (similar and even higher than nystatin) against all C. albicans isolates with minimal inhibitory concentration (MIC) = 0.008-7.81 µg/mL Their mechanism of action may be related to action within the fungal cell wall structure and/or within the cell membrane. The interactions between the derivatives and the selected antimycotics (nystatin, chlorhexidine, and thymol) showed additive effect only in the case of combination some of them and thymol. The erythrocyte lysis assay confirmed the low cytotoxicity of these compounds as compared to nystatin. The high lipophilicity of the derivatives was related with their high antifungal activity. The present studies confirm that the studied thiazole derivatives containing the cyclopropane system appear to be a very promising group of compounds in treatment of infections caused by C. albicans. However, this requires further studies in vivo. KEY POINTS: • The newly thiazoles showed high antifungal activity and some of them - additive effect in combination with thymol. • Their mode of action may be related with the influence on the structure of the fungal cell wall and/or the cell membrane. • The low cytotoxicity against erythrocytes and high lipophilicity of these derivatives are their additional good properties.
Keyphrases
- candida albicans
- cell wall
- biofilm formation
- structure activity relationship
- end stage renal disease
- risk assessment
- ejection fraction
- high throughput
- case control
- newly diagnosed
- escherichia coli
- stem cells
- chronic kidney disease
- mass spectrometry
- peritoneal dialysis
- cystic fibrosis
- intensive care unit
- staphylococcus aureus
- cell therapy
- ms ms
- smoking cessation
- high speed
- patient reported
- respiratory failure
- tandem mass spectrometry
- drug induced
- acute respiratory distress syndrome
- extracorporeal membrane oxygenation