The newly synthesized thiazole derivatives as potential antifungal compounds against Candida albicans

Abstract

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. Graphical abstract

A Cecropin-4 Derived Peptide C18 Inhibits Candida albicans by Disturbing Mitochondrial Function

“…has increased dramatically, especially in immunocompromised patients (Houšt' et al, 2020). Candida albicans (C. albicans), the predominant fungi, has been reported to account for as high as 35-50% of mortality rate in candidiasis (Biernasiuk et al, 2021). However, other emerging drugresistant Candida species-non-albicans Candida spp.…”

Antifungal Activity of the Frog Skin Peptide Temporin G and Its Effect on Candida albicans Virulence Factors

“…Ergosterol is a well-known component of the fungal cell membrane, and it is an important target of many antifungal drugs [ 36 ]. We, therefore, investigated the possible binding of TG to ergosterol, by evaluating the MIC of the peptide in the presence of exogenous ergosterol (see Section 4 ) [ 37 , 38 ]. As shown in Figure 4 , the MIC of TG remained unchanged, while the MIC of amphotericin B, a well-known antifungal drug that interacts with the cell membrane ergosterol [ 36 ], was enhanced in parallel with increasing concentrations of exogenous ergosterol.…”

Electrochemical studies: Biological evaluation of the homometallic‐binuclear complexes of malonate‐derived tetradentate O2N2 ligand

“…When compared to the free NO 3 À group (1700-1800 cm À1 ), these three bands that characterize the unidentate nitrate group were noticeably displaced to lower frequencies. 1,14,55 This shift is a result of the movement of electron flow from NO 3 À to the metal ions, and this could serve as an indicator for the covalent bond's strength. Moreover, the nitrate group exists as a free ion attached to all coordination compounds whose vibrations appear in the 1759-1763 and 1361-1354 cm À1 regions.…”