Cytotoxic and Antibacterial Prenylated Acylphloroglucinols from Hypericum olympicum L.

Abstract

Two new bicyclo[3.3.1]nonane type bicyclic polyprenylated acylphloroglucinol derivatives (BPAPs), olympiforin A and B as well as three known prenylated phloroglucinols, were isolated from the aerial parts of Hypericum olympicum L. The structures of the isolated compounds were established by means of spectral techniques (HRESIMS and 1D and 2D NMR). All compounds were tested on a panel of human tumor (MDA-MB-231, EJ, K-562, HL-60 and HL-60/DOX) and non- tumorigenic (HEK-293 and EA.hy926) cell lines using the MTT assay. All tested compounds exerted significant in vitro cytotoxicity with IC50 values ranging from 1.2 to 24.9 μM and from 0.9 to 34 μM on tumor and non-cancerous cell lines, respectively. Most of the compounds had good selectivity and were more cytotoxic to the tumor cell lines than to the normal ones. A degradation of the precursor caspase 9 for some of the compounds was observed; therefore, the intrinsic pathway of apoptosis is the most likely mechanism of cytotoxic activity. The BPAPs were examined for antibacterial and antibiofilm activity through the broth microdilution method and the protocol of Stepanović. They showed a moderate effect against Enterococcus faecalis and Streptococcus pyogenes but a very profound activity against Staphylococcus aureus with minimum inhibitory concentrations (MIC) in the range of 0.78–2 mg/L. Olympiforin B also had a great effect against methicillin-resistant S. aureus (MRSA) with an MIC value of 1 mg/L and a very significant antibiofilm activity on that strain with a minimum biofilm inhibition concentration (MBIC) value of 0.5 mg/L. The structures of the isolated compounds were in silico evaluated using ADME and drug likeness tests.