Undescribed phloroglucinol derivatives with antiviral activities from Dryopteris atrata (Wall. Ex Kunze) Ching. (April 2023) - Zhang, Ji-hui
Abstract: Nine undescribed phloroglucinol derivatives (dryatraols A-I) with five different backbones and three known dimeric acylphloroglucinols were isolated from the rhizome of Dryopteris atrata (Wall. Ex Kunze) Ching (Dryopteridaceae). Dryatraol A contains an unprecedented carbon skeleton—a butyrylphloroglucinol and a rulepidanol-type sesquiterpene are linked via a furan ring to form a 6/5/6/6 ring system. Dryatraols B and C are the first examples of monomeric phloroglucinols coupled with the aristolane-type sesquiterpene through the C–C bond. Dryatraol D features a rare spiro [benzofuran-2′, 5″-furan] backbone. Dryatraols E-I are five undescribed adducts with a butyrylphloroglucinol or filicinic acid incorporated into the germacrene-type sesquiterpene via a pyran ring. These undescribed structures were determined by comprehensively analysing the spectroscopic data, X-ray diffraction results, and electronic circular dichroism calculations. The result of in vitro antiviral activity evaluation indicated that dryatraol C displayed the strongest antiviral effect against both respiratory syncytial virus and influenza A virus (H1N1), with IC50 values of 11.9 μM and 5.5 μM, respectively. Dryatraols F–H exhibited considerable inhibitory activity against herpes simplex virus type 1 (HSV-1), with IC50 values ranging from 2.6 to 6.3 μM. Analysis of the inhibitory mechanism using a time-of-addition assay revealed that dryatraol G may inhibit the replication of HSV-1 by interfering with the late stage of the viral life cycle. Graphical abstract: Nine undescribed phloroglucinol derivatives were isolated from Dryopteris atrata, and some of them displayed significant anti-HSV-1 and anti-H1N1 activities. Time-of-addition test indicated that dryatraol G might inhibit the late stage of HSV-1 replication. Image 1 Highlights: Nine undescribed phloroglucinol derivatives were isolated from Dryopteris atrata. Dryatraol A represents the first example of an acylphloroglucinol-rulepidanol adduct. Dryatraol D possesses a rare spiro [benzofuran-2′, 5″-furan] backbone. Most isolates were evaluated for antiviral activities against three common viruses. A few isolates showed comparable antiviral effect to the positive controls.