Four new cytotoxic polyprenylated acylphloroglucinols from Hypericum barbatum Jacq.

Polycyclic polyprenylated acylphloroglucinols (PPAPs) are one of the most interesting compounds from Hypericum species. Their biological and pharmacological activity is varying largely due to the possibilities of prenylation, cyclization and oxydation. Among other activities, antidepressant, analgesic, antioxidative, anti-inflammatory, antimicrobial and cytotoxic are predominantly related with PPAPs[1]. This increases the interest for discovery and isolation of new acylphloroglucinols and testing their biological abilities. H. barbatum Jacq. is a plant distributed widely throughout Europe, from Austria to Greece, through Balkans and Mediterranean regions[2]. Being poorly investigated regarding its PPAP spectrum, it represents an interesting source for phytochemical research. Using ¹H-NMR guided fractionation of its aerial parts' petrol ether extract, four novel tricyclic polyprenylated, endoperoxide bridge-containing acylphloroglucinols, hyperibarbins A-D (1-4) were isolated. Their structures were elucidated using 2D NMR spectroscopic data and HRESIMS. Cytotoxic activity was evaluated against HepG2 liver tumor cells, HeLa cervix epitheloid carcinoma, PC-3 prostate tumor cells, A549 lung tumor cell lines and MRC-5 healthy human fetal lung cells, with the four compounds exhibiting moderate cytotoxicity against all examined cell lines. IC₅₀ values were 9.22 – 17.0µM for HepG2, 12.8 – 21.8µM to inhibit growth of HeLa cells, 14.4 – 27.8µM for PC-3 tumor cells and 20.2 – 27.1µM for A549 lung tumor cells. Unfortunately, they were also toxic for the human fibroblast lung cell line MRC-5, with IC₅₀ 13.4 – 20.4µM. Similarity in action is noted among the analogous hyperibarbins A (1) and C (3), as well as B (2) and D (4).

Fig. 1

[1] Zhao J, Liu W, Wang JC. Chem Biodiv 2015; 12: 309 – 349;

[2] Robson NKB. Phytotaxa 2012; 72: 1 – 111.