Aspermerodione, a novel fungal metabolite with an unusual 2,6-dioxabicyclo[2.2.1]heptane skeleton, as an inhibitor of penicillin-binding protein 2a

Abstract

Rising drug resistance limits the treatment options infected by methicillin-resistant Staphylococcus aureus (MRSA). A promising solution for overcoming the resistance of MRSA is to inhibit the penicillin-binding protein 2a (PBP2a). A novel terpene-polyketide hybrid meroterpenoid, aspermerodione (1), characterized by an unusual 2,6-dioxabicyclo[2.2.1]heptane core skeleton, and a new heptacyclic analogue, andiconin C (2), were isolated and identified from the liquid cultures of endophytic fungus Aspergillus sp. TJ23. The structures and their absolute configurations of all chiral centers were elucidated via extensive spectroscopic analyses and electronic circular dichroism (ECD) calculations and determined via single-crystal X-ray diffraction analysis. Aspemerodione (1) was found to be a potential inhibitor of PBP2a, and work synergistically with the β-lactam antibiotics oxacillin and piperacillin against MRSA.

Progress on Terpenoids With Biological Activities Produced by Plant Endophytic Fungi in China Between 2017 and 2019

“…TJ23. 65 Aspemerodione (189) was found to be a potential inhibitor of PBP2a and worked synergistically with the β-lactam antibiotics oxacillin and piperacillin against MRSA (Methicillin-resisitant Staphylococcus Aureus). 65 Polyketide-terpenoids have also been identified in Penicillium (Figure 12).…”

“…65 Aspemerodione (189) was found to be a potential inhibitor of PBP2a and worked synergistically with the β-lactam antibiotics oxacillin and piperacillin against MRSA (Methicillin-resisitant Staphylococcus Aureus). 65 Polyketide-terpenoids have also been identified in Penicillium (Figure 12). Isopenicins A-C (190-192), 3 meroterpenoids possessing 2 types of terpenoid-polyketide hybrid skeletons, were isolated from cultures of the Penicillium sp.…”

Asperversins A and B, Two Novel Meroterpenoids with an Unusual 5/6/6/6 Ring from the Marine-Derived Fungus Aspergillus versicolor

“…During our investigation of bioactive metabolites from fungi [ 15 , 16 , 17 , 18 , 19 ], many novel meroterpenoids were isolated from various fungi. Asperterpene A, obtained from Aspergillus terreus , represents a potential lead compound and a versatile scaffold for the development of drugs for the treatment of Alzheimer’s disease [ 15 ].…”

Polyketide and Prenylxanthone Derivatives from the Endophytic Fungus Aspergillus sp. TJ23

“…TJ23, an endophytic fungus belong to the Aspergillus family, was isolated from the medicinal plant Hypericum perforatum L. Our previous studies on the secondary metabolites of this strain under different cultural conditions had led to the isolation of several novel and bioactive compounds. For example, two terpene-polyketide hybrid meroterpenoids, spiroaspertrione A [4] and aspermerodione [5] were found to be potential inhibitors of methicillin-resistant Staphylococcus aureus (MRSA).…”

“…TJ23 was chemically re-investigated. This work gave rise to the isolation and characterization of two new compounds, asperetide (1) and asperanthone (4), and six known compounds, (S)-3butyl-7-methoxyphthalide (2), [10] ruguloxanthone C (3), [11] tajixanthone hydrate (5), [12] tajixanthone methanoate (6), [13] salimyxin B (7), [14] and ergosterol (8; Figure 1). [15] Herein, we described the isolation, structural determination, and biological activity evaluation of the isolates.…”