Azole-Based Compounds That Are Active against Candida Biofilm: In Vitro, In Vivo and In Silico Studies

Abstract

Fungal pathogens, including Candida spp., Aspergillus spp. and dermatophytes, cause more than a billion human infections every year. A large library of imidazole- and triazole-based compounds were in vitro screened for their antifungal activity against C. albicans, C. glabrata, C. krusei, A. fumigatus and dermatophytes, such as Microsporum gypseum, Trichophyton rubrum and Trichophyton mentagrophytes. The imidazole carbamate 12 emerged as the most active compound, showing a valuable antifungal activity against C. glabrata (MIC 1–16 μg/mL) and C. krusei (MIC 4–24 μg/mL). No activity against A. fumigatus or the dermatophytes was observed among all the tested compounds. The compound 12 inhibited the formation of C. albicans, C. glabrata and C. krusei biofilms and reduced the mature Candida biofilm. In the Galleria mellonella larvae, 12 showed a significant reduction in the Candida infection, together with a lack of toxicity at the concentration used to activate its antifungal activity. Moreover, the in silico prediction of the putative targets revealed that the concurrent presence of the imidazole core, the carbamate and the p-chlorophenyl is important for providing a strong affinity for lanosterol 14α-demethylase (CgCYP51a1) and the fungal carbonic anhydrase (CgNce103), the S-enantiomer being more productive in these interactions.

New Anthranilic Acid Hydrazones as Fenamate Isosteres: Synthesis, Characterization, Molecular Docking, Dynamics & in Silico ADME, in Vitro Anti‐Inflammatory and Anticancer Activity Studies

“…The simulation was run, with a time step of 2.5 fs and using the RESPA integrator. The interactions between the ligand and protein during the binding were analyzed, as well as the RMSD, of the Cα atoms of the protein and the heavy atoms of the ligand, by utilizing Desmond [52,53] …”

3‐Amino‐thiophene‐2‐carbohydrazide Derivatives as Anti Colon Cancer Agents: Synthesis, Characterization, In‐Silico and In‐Vitro Biological Activity Studies

“…The interactions between the ligand and protein during the binding were analyzed, as well as the RMSD, of the Cα atoms of the protein and the heavy atoms of the ligand, by utilizing Desmond. [35][36][37][38]…”

Emergence and circulation of azole-resistant C. albicans, C. auris and C. parapsilosis bloodstream isolates carrying Y132F, K143R or T220L Erg11p substitutions in Colombia

“…While current therapeutic options for IFIs are limited to only three classes of drugs (i.e., polyenes, azoles and echinocandins), the emergence of resistant strains to some of these molecules is even more concerning. For decades, azoles have been the most frequently used antifungal for treating Candida infections ( Sheehan et al., 1999 ; Carradori et al., 2022 ). Although treatment with azoles can be effective, long-term use of fluconazole (FLC) has led to the emergence of Candida strains with decreased susceptibility.…”