Antifungal Agents: Design, Synthesis, Antifungal Activity and Molecular Docking of Phloroglucinol Derivatives

Abstract

Pseudoaspidinol is a phloroglucinol derivative with Antifungal activity and is a major active component of Dryopteris fragrans. In our previous work, we studied the total synthesis of pseudoaspidinol belonging to a phloroglucinol derivative and investigated its antifungal activity as well as its intermediates. However, the results showed these compounds have low antifungal activity. In this study, in order to increase antifungal activities of phloroglucinol derivatives, we introduced antifungal pharmacophore allylamine into the methylphloroglucinol. Meanwhile, we remained C1–C4 acyl group in C-6 position of methylphloroglucinol using pseudoaspidinol as the lead compound to obtain novel phloroglucinol derivatives, synthesized 17 compounds, and evaluated antifungal activities on Trichophyton rubrum and Trichophyton mentagrophytes in vitro. Molecular docking verified their ability to combine the protein binding site. The results indicated that most of the compounds had strong antifungal activity, in which compound 17 were found to be the most active on Trichophyton rubrum with Minimum Inhibitory Concentration (MIC) of 3.05 μg/mL and of Trichophyton mentagrophytes with MIC of 5.13 μg/mL. Docking results showed that compounds had a nice combination with the protein binding site. These researches could lay the foundation for developing antifungal agents of clinical value.

Isoflavaspidic Acid PB Extracted from Dryopteris fragrans (L.) Schott Inhibits Trichophyton rubrum Growth via Membrane Permeability Alternation and Ergosterol Biosynthesis Disruption

“…SE and CYP51 are among the key enzymes in the ergosterol biosynthesis pathway [53]. For most of fungi, SE is a flavin adenine dinucleotide (FAD) that catalyses the epoxidation of squalene to 2,3-oxidosqualene, thereby leading to a cascade of ergosterol biosynthetic pathways [55]. TBF is active when administrated either topically or orally.…”

Flow Hydrogenation of 1,3,5-Trinitrobenzenes over Cu-Based Catalysts as an Efficient Approach for the Preparation of Phloroglucinol Derivatives

“…3 In addition, 2-methylphloroglucinol and 2,4-dimethylphloroglucinol have been obtained through the Vilsmeier–Haack reaction of phloroglucinol with subsequent reduction. 1a h i But this approach is inefficient because of the use of expensive phloroglucinol as a raw material.…”

New Anticancer Agents: Design, Synthesis, Biological Activity, and Molecular Docking of Bicyclic Phloroglucinol Derivatives

“…In previous studies, we have completed the total synthesis, derivatization, and activity evaluation of some monocyclic phloroglucinols and noticed that the monocyclic derivatives have a variety of biological activities [19,20] . In this study, in order to obtain more excellent antitumor activity, we have made a number of modifications around the scaffold of flavaspidic acid ( AB ) and albaspidin ( AA ) (Figure 1).…”