Discovery of structurally diverse polyprenylated acylphloroglucinols with quorum sensing inhibitory activity from Hypericum seniawinii Maxim

TL;DR

Researchers discovered new compounds from a plant that can inhibit bacterial communication, potentially useful for fighting infections.

Contribution

Identification of structurally diverse polyprenylated acylphloroglucinols with quorum sensing inhibition from Hypericum seniawinii.

Findings

Hyperisenins A–D are new polyprenylated acylphloroglucinols with unique structural features.

Compound 4 inhibits quorum sensing in Pseudomonas aeruginosa by reducing rhamnolipid levels.

Compound 4 may bind to lasR and pqsR to disrupt bacterial communication.

Abstract

Four previously undescribed polyprenylated acylphloroglucinols, hyperisenins A–D (1–4), along with two known analogues (5 and 6), were obtained from the aerial part of Hypericum seniawinii Maxim. Compounds 1 and 2 were two highly degraded polyprenylated acylphloroglucinols with a cyclohexanone-monocyclic skeleton, while compound 3 was the first example of O-prenylated acylphloroglucinols with a 6/6/6 ring system. Their structures were identified by analyzing NMR, HRESIMS data, and quantum chemical calculations. The biosynthetic pathway of 1 and 2 might originate from bicyclic polyprenylated acylphloroglucinols via a series of complex retro-Claisen, keto − enol tautomerism, and intramolecular cyclization. The bioassay results showed that 4 exhibited quorum sensing inhibitory activity against Pseudomonas aeruginosa, which could decrease the activation of the rhl system, and significantly reduce rhamnolipid levels at a concentration of 100 µM, and the mechanism might be the ability to bind 4 to lasR and pqsR.

The online version contains supplementary material available at 10.1007/s13659-025-00520-z.

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