New thymol-derived triazole exhibits promising activity against Trichophyton rubrum

• Published in: Brazilian journal of microbiology Vol. 55; no. 2; pp. 1287 - 1295
• Main Authors: de Sousa Cutrim, Thiago Antonio, Eloy, Mariana Alves, Barcelos, Fernando Fontes, Meireles, Leandra Martins, de Freitas Ferreira, Lara Chaves, Reis, Tatiana Alves, Gonçalves, Sarah Santos, Lacerda, Valdemar, Fronza, Marcio, Morais, Pedro Alves Bezerra, Scherer, Rodrigo
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-06-2024
• Subjects: Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Arthrodermataceae - drug effects; Arthrodermataceae - genetics; Aspergillus fumigatus - drug effects; Aspergillus fumigatus - genetics; Biomedical and Life Sciences; Candida albicans - drug effects; Candida albicans - genetics; Clinical Microbiology - Research Paper; Food Microbiology; Humans; Keratinocytes - drug effects; Life Sciences; Medical Microbiology; Microbial Ecology; Microbial Genetics and Genomics; Microbial Sensitivity Tests; Microbiology; Molecular Docking Simulation; Mycology; Saccharomyces cerevisiae - drug effects; Saccharomyces cerevisiae - genetics; Thymol - chemistry; Thymol - pharmacology; Triazoles - chemistry; Triazoles - pharmacology; Trichophyton - drug effects; Trichophyton - genetics; Thymol; Triazole; Aspergillus; Trichophyton rubrum; Candida
• ISSN: 1517-8382; 1678-4405; 1678-4405
• DOI: 10.1007/s42770-024-01295-0

Fungal infections have emerged worldwide, and azole antifungals are widely used to control these infections. However, the emergence of antifungal resistance has been compromising the effectiveness of these drugs. Therefore, the objective of this study was to evaluate the antifungal and cytotoxic activities of the nine new 1,2,3 triazole compounds derived from thymol that were synthesized through Click chemistry. The binding mode prediction was carried out by docking studies using the crystallographic structure of Lanosterol 14α-demethylase G73E mutant from
Saccharomyces cerevisiae
. The new compounds showed potent antifungal activity against
Trichophyton rubrum
but did not show relevant action against
Aspergillus fumigatus
and
Candida albicans
. For
T. rubrum
, molecules nº 5 and 8 showed promising results, emphasizing nº 8, whose fungicidal and fungistatic effects were similar to fluconazole. In addition, molecule nº 8 showed low toxicity for keratinocytes and fibroblasts, concluding that this compound demonstrates promising characteristics for developing a new drug for dermatophytosis caused by
T. rubrum
, or serves as a structural basis for further research.