Fifteen new depsidone-based analogues named spiromastixones A-O (1-15) were isolated from the fermentation broth of a deep-sea Spiromastix sp. fungus. Their structures were elucidated on the basis of extensive NMR and mass spectroscopic analysis in association with chemical conversion. Spiromastixones A-O are classified into two subtypes based on the orientation of ring C relative to ring A, while the n-propyl substituents on rings A and C are rarely seen in natural products. Most analogues are substituted by various numbers of chlorine atoms. All compounds exhibited significant inhibition against Gram-positive bacteria including Staphylococcus aureus, Bacillus thuringiensis, and Bacillus subtilis with MIC values ranging from 0.125 to 8.0 μg/mL. In addition, compounds 6-10 displayed potent inhibitory effects against methicillin-resistant bacterial strains of S. aureus (MRSA) and S. epidermidis (MRSE), while 10 also inhibited the growth of the vancomycin-resistant bacteria Enterococcus faecalis and E. faecium (VRE). The structure-activity relationships are discussed.
