Prenylated acylphloroglucinols from aerial parts of Hypericum scabrum

Abstract

Hypericum is one of the biggest genus of family Hypericasease, with multifarious applications in traditional medicine around the world. H. scabrum, one of the species of Hypericum, growing in Iran, has been used in Iranian folk medicine as an antiseptic, a sedative, an analgesic, and for the treatment of headaches [1]. Several classes of compounds were reported from Hypericum genus, and polyprenylated acylphloroglucinols (PPAPs) are among those well-known secondary metabolites isolated from this genus to date. The structural diversity of above-mentioned compounds leads to broad ranges of bioactivity observed for them including anti-depressant, anti-HIV, anti-neurodegenerative, and anti-inflammatory [2]. MS-based analysis of the fractions obtained from chromatographical separation of the methanolic extract of H. scabrum displayed the presence of new phloroglucinol derivatives. Therefore, this work aimed for i) isolation of new phloroglucinols from the aerial parts of H. scabrum, ii) investigation of their inhibitory activity against 5-lipoxygenase (5-LOX), and iii) deciphering their absolute configuration using chiroptical and computational approaches. Five new prenylated acylphloroglucinols along with two known ones are reported (example scaffold below), the structures of which established using 1&2D NMR and HRMS, and their absolute configuration determined using electronic circular dichroism (ECD) and quantum chemical calculations. Investigation of their 5-LOX inhibitory activity at a single concentration of 10 µM revealed that only compounds 3 and 4 have moderate activity in cell free assays; however, no activity was observed on human neutrophils.