Preparation, Antidermatophyte Activity, and Mechanism of Methylphloroglucinol Derivatives

Abstract

In this study a variety of phloroglucinols were isolated from the plant, and the activity experiment showed that the phloroglucinols had strong antifungal activity, especially methylphloroglucinol derivatives such as aspidin PB, dryofragin, aspidinol, aspidin BB, aspidin AB, and albicanol, in which the hydroxyl group of methylphloroglucinol is the active group of compounds, and C-2 or C-6 is the active site. The introduction of different groups in this position could change the properties and bioactivity of the compounds. In this study, different functional groups were introduced to the structure of methylphloroglucinol to obtain methylphloroglucinol derivatives that were synthesized, and antidermatophyte activities on Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum canis, and Gypsum microspore bacteria were evaluated. Molecular docking verified its ability to combine the protein binding site. The antidermatophyte mechanism of compounds on cytochrome P450 sterol 14a-demethylase, squalene epoxidase, and β-1,3-glucan synthase was investigated by the enzyme-linked immunosorbent assay. The results showed that compounds had an inhibitory effect on four kinds of common dermatophytes in varying degrees, in which compound g had the strongest activities, the binding mode of methylphloroglucinol and its derivatives were similar to those of three enzymes, and compounds e and g had significant effects on the activity of the three enzymes, and compound g had a slightly stronger effect than the blank group. Compounds e and g also had a significant effect on the ergosterol synthesis of M. canis. This study could supply some antidermatophyte leading structure and possible mechanism for studying and developing new antifungal agents.

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

“…Methylphloroglucinol derivatives had been reported to reduce ergosterol content by inhibiting the activities of SE and CYP51 in M. canis [60]. This result corroborates with that presented above, which can justify ergosterol biosynthesis interference resulting from inhibition of sterol metabolismrelated enzymes.…”

Phloroglucinol and Its Derivatives: Antimicrobial Properties toward Microbial Pathogens

“…Chemical derivatization reaction involved in the synthesis of different types of phloroglucinol derivatives: (A) MP4, (B) formyl phloroglucinol meroterpenoid compound c2, , (C) methylphloroglucinol derivatives such as compounds e, f, and g, and (D) compound 17 from PG . MSA, methanesulfonic acid; DMF, dimethylformamide; PEG, poly­(ethylene glycol); [4 + 2], Diels–Alder reaction.…”

“…The presence of two methylphloroglucinol derivatives named compound e and g at 1/2-MIC and MIC have shown strong antidermatophyte activity against Microsporum canis cell membrane and cell wall, which was due to decreasing ergosterol biosynthesis and inhibition of β-1,3-glucan synthase, squalene epoxide (SE), and sterol 14α-demethylase cytochrome P450 (CYP51) via strong binding energy to the protein binding sites . According to Ye et al, the synthesis of compounds g and e occurs from a methylphloroglucinol substrate, which is produced from PG via the Vilsmeier–Haack reaction and reduction reaction, followed by various additional steps (Figure C).…”

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).…”