Abstract
In our ongoing search for new bioactive fungal metabolites, four previously undescribed oxazole carboxylic acid derivatives (1–4) for which we proposed the trivial names macrooxazoles A–D together with two known tetramic acids (5–6) were isolated from the plant pathogenic fungus Phoma macrostoma. Their structures were elucidated based on high-resolution mass spectrometry (HR-MS) and nuclear magnetic resonance (NMR) spectroscopy. The hitherto unclear structure of macrocidin Z (6) was also confirmed by its first total synthesis. The isolated compounds were evaluated for their antimicrobial activities against a panel of bacteria and fungi. Cytotoxic and anti-biofilm activities of the isolates are also reported herein. The new compound 3 exhibited weak-to-moderate antimicrobial activity as well as the known macrocidins 5 and 6. Only the mixture of compounds 2 and 4 (ratio 1:2) showed weak cytotoxic activity against the tested cancer cell lines with an IC50 of 23 µg/mL. Moreover, the new compounds 2 and 3, as well as the known compounds 5 and 6, interfered with the biofilm formation of Staphylococcus aureus, inhibiting 65%, 75%, 79%, and 76% of biofilm at 250 µg/mL, respectively. Compounds 5 and 6 also exhibited moderate activity against S. aureus preformed biofilm with the highest inhibition percentage of 75% and 73% at 250 µg/mL, respectively.
Highlights
Oxazole and its derivatives are heterocyclic systems which have gained strong interest in recent times due to their increasing importance in the field of medicinal chemistry [1]
As part of our ongoing search of exploring fungi for new biologically active metabolites, we investigated the chemical components of the fermentation extract of the plant pathogenic fungus Phoma macrostoma originally isolated from its host, the noxious weed, Cirsium arvense
high performance liquid chromatography (HPLC) led to the isolation of four previously undescribed metabolites (1–4), together with two known compounds, the macrocidins A (5) and Z (6) (Figure 2)
Summary
Oxazole and its derivatives are heterocyclic systems which have gained strong interest in recent times due to their increasing importance in the field of medicinal chemistry [1] They feature a well-known important doubly unsaturated 5-membered ring heterocyclic motif having one oxygen atom at position 1 and a nitrogen at position 3 separated by a carbon in between [2]. Their widespread useful biological activities including antimicrobial [3], anticancer [4], antitubercular [5], anti-inflammatory [6], antidiabetic [7], antiobesity [8] and anthelminthic [9] effects have attracted increasing attention of chemical and pharmacological communities in their search for new lead compounds [1]. Four previously undescribed oxazole-4-carboxylic acid derivatives (1–4) together with two known macrocidins (5–6)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
