Abstract
Fungal natural products play a prominent role in the development of pharmaceuticalagents. Two new cyclic tetrapeptides (CTPs), westertide A (1) and B (2), with eight known compounds (3–10) were isolated from the fungus Aspergillus westerdijkiae guided by OSMAC (one strain-many compounds) and molecular networking strategies. The structures of new compounds were unambiguously determined by a combination of NMR and mass data analysis, and chemical methods. All of the isolates were evaluated for antimicrobial effects, synergistic antifungal activity, cytotoxic activity, and HDAC inhibitory activity. Compounds 1–2 showed synergistic antifungal activity against Candida albicans SC5314 with the presence of rapamycin and weak HDAC (histone deacetylase) inhibitory activity. These results indicate that molecular networking is an efficient approach for dereplication and identification of new CTPs. CTPs might be a good starting point for the development of synergistic antifungal agents.
Highlights
Fungal natural products play a prominent role in the development of pharmaceutical agents [1,2]
A molecular networking-one strain-many compounds (OSMAC) strategy was applied to accelerate the discovery of cyclic tetrapeptides
The fungus A. westerdijkiae L1295 was fermented in different culture media and conditions using the OSMAC method (Table S1)
Summary
Fungal natural products play a prominent role in the development of pharmaceutical agents [1,2]. Cyclic tetrapeptides (CTPs) are a type of important bioactive natural product that were found to have a broad range of pharmacological properties, including antimicrobial [3,4], cytotoxic [5,6,7], and HDAC (histone deacetylase) inhibitory properties [8]. Some naturally occurring CTPs have been found to inhibit HDAC and regulate gene expression, which are very useful as cancer therapeutics. Occurring CTPs are usually produced in low yields, which limits the discovery of new CTPs. MS/MS-based molecular networking paves the way to solving this problem. In the field of bioactive peptides discovery, neoantimycin L with excellent cytotoxicity from Streptomyces conglobatus RJ8 [16] and thermoactinoamide A with moderate antiproliferative activity from Thermoactinomyces vulgaris DSM 43016 [17] were obtained based on molecular networking
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