Pitsubcosides M−S: Novel antibacterial cadinane sesquiterpenoid glycoside esters from Pittosporum subulisepalum

Abstract

A previous study on Pittosporum subulisepalum led to twelve novel, antibacterial eudesmane sesquiterpenoid glycoside esters (ESGEs). To continue the work on P. subulisepalum, this study focused on the exploration of cadinane sesquiterpenoid glycoside esters (CSGEs) with antibacterial activities and their mechanism of actions. Chemical exploration of the ethyl acetate (EtOAc) soluble phase of the leaves and stems of P. subulisepalum resulted in seven previously unreported cadinane sesquiterpenoid glycosides (CSGs), pitsubcosides M-S (1 −7), along with three known analogs. Based on one- and two-dimensional NMR (1D and 2D NMR), HRESIMS, and experimental/calculated electronic circular dichroism (ECD) spectroscopic analyses, the structures of the isolated compounds were elucidated. The novelty of these sesquiterpenoid glycosides was characterized by the highly esterified glycoside moieties. Compounds 1 − 5 exhibited marked inhibitory effects on Bacillus subtilis, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Bacillus cereus, Erwinia carotovora, and Pseudomonas syringae pv. actinidiae with the minimum inhibitory concentration (MIC) values of 3.13 μM− 50 μM. Of these, compounds 1 − 2 displayed significant antibacterial activity against B. subtilis (MIC = 3.13 and 6.25 μM). The live masses and the biofilms of B. subtilis were quantified after being treated with compounds 1 and 2. The preliminary antibacterial mechanism was revealed as to prevent bacterial biofilm formation or to destroy the formed cell membranes. These results indicated that CSGEs from P. subulisepalum are potential antibacterial lead agents.