Design, synthesis, docking studies and bioactivity evaluation of 1,2,3-triazole eugenol derivatives
Creators: name: de Sousa Cutrim, Thiago Antonio
name: Barcelos, Fernando Fontes
name: Meireles, Leandra Martins
name: Gazolla, Poliana Aparecida Rodrigues
name: Lima, Ângela Maria Almeida
name: Teixeira, Róbson Ricardo
name: Moreira, Luiza Carvalheira
name: de Queiroz, Vagner Tebaldi
name: Barbosa, Luiz Cláudio Almeida
name: Morais, Pedro Alves Bezerra
name: do Nascimento, Cláudia Jorge
name: Junker, Jochen
name: Costa, Adilson Vidal
name: Fronza, Marcio
name: Scherer, Rodrigo
Publisher: name: Taylor & Francis
Year: 2024
Subjects: Biophysics
Biochemistry
Pharmacology
Biotechnology
Chemical Sciences not elsewhere classified

description: <b>Aim:</b> The design, synthesis, docking studies and evaluation of the <i>in vitro</i> antifungal and cytotoxic properties of eugenol (EUG) containing 1,2,3-triazole derivatives are reported. Most of the derivatives have not been reported. <b>Materials &amp; methods:</b> The EUG derivatives were synthesized, molecular docked and tested for their antifungal activity. <b>Results:</b> The compounds showed potent antifungal activity against <i>Trichophyton rubrum</i>, associated with dermatophytosis. Compounds <b>2a</b> and <b>2i</b> exhibited promising results, with <b>2a</b> being four-times more potent than EUG. The binding mode prediction was similar to itraconazole in the lanosterol-14-α-demethylase wild-type and G73E mutant binding sites. Additionally, the pharmacokinetic profile prediction suggests good gastrointestinal absorption and potential oral administration. <b>Conclusion:</b> Compound <b>2a</b> is a promising antifungal agent against dermatophytosis caused by <i>T. rubrum</i>. This study describes the synthesis, antifungal activity evaluation and docking studies of a series of eugenol (EUG)-containing 1,2,3-triazole derivatives. The synthesis of the compounds was achieved in two steps, namely propargylation of EUG followed by the Cu(I)-catalyzed azide–alkyne cycloaddition reactions between the propargylated EUG and different commercially avaialable phenyl azides. The identities of the compounds were confirmed by <sup>1</sup>H and <sup>13</sup>C nuclear magnetic resonance and Infrared spectroscopies along with Mass spectrometry. The EUG derivatives were evaluated against <i>Aspergillus flavus</i> ATCC 204304, <i>A. fumigatus</i> ATCC 16913, <i>Trichophyton rubrum</i> CCT 5506 and <i>Candida albicans</i> ATCC 10231. The best results concerning antifungal activity were noted for compounds 4-((4-allyl-2-methoxyphenoxy)methyl)-1-(4-bromophenyl)-1<i>H</i>-1,2,3-triazole (<b>2a</b>) and 4-((4-allyl-2-methoxyphenoxy)methyl)-1-(2-fluorophenyl)-1<i>H</i>-1,2,3-triazole (<b>2i</b>), which demonstrated significant activity against the dermatophyte <i>T. rubrum</i>, with MIC values of 16 and 32 μg ml<sup>-1</sup>, respectively. The docking study involving compounds <b>2a</b> and <b>2i</b> revealed a behavior similar to itraconazole in the lanosterol-14α-demethylase wild-type and G73E mutant binding site. In addition, the pharmacokinetic profile prediction suggests good gastrointestinal aborption and potential oral administration for these compunds.