Polycyclic polyprenylated acylphloroglucinols: natural phosphodiesterase-4 inhibitors from Hypericum sampsonii. Issue 58 (2nd June 2016)

• Record Type: Journal Article
• Authors: Zhang, Jun-Sheng; Zou, Yi-Hong; Guo, Yan-Qiong; Li, Zhen-Zhen; Tang, Gui-Hua; Yin, Sheng
• Is Part Of: RSC advances. Volume 6:Issue 58(2016)
• Page Start: 53469
• Page End: 53476
• Publication Date: 2016-06-02
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c6ra08805h
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : Seven novel PPAPs and 23 known analogs were isolated from Hypericum sampsonii, some of which were identified as potent PDE4 inhibitors. Abstract : Chemical investigation of the aerial parts of Hypericum sampsonii led to the isolation of seven new polycyclic polyprenylated acylphloroglucinols, hypersampsonones A–G (1–7 ), together with 23 known analogs (8–30 ). Their structures including the absolute configurations were elucidated by combined spectroscopic analysis, quantum chemical ECD calculations, and chemical methods. Compound1 represents an unprecedented cyclocitral monoterpene-coupled bicyclo[3.3.1]nonane skeleton, while2 features an unusual hexahydrofuro[2, 3- b ]furan-diepoxy ring system fused in a tricyclo[4.3.1.1 5, 7 ]undecane skeleton. All the compounds were screened by using tritium-labeled adenosine 3′, 5′-cyclic monophosphate ([ 3 H]-cAMP) as substrate for their inhibitory activity against phosphodiesterase-4 (PDE4), which is a drug target for the treatment of asthma and chronic obstructive pulmonary disease. Compounds1, 18–19, 21, and25–30 exhibited inhibition with IC50 values less than 10 μM, in which compound19 represented the most active compound (IC50 = 0.64 μM), being comparable to the positive control, rolipram (IC50 = 0.62 μM).