Antibacterial Indole Diketopiperazine Alkaloids from the Deep-Sea Cold Seep-Derived Fungus Aspergillus chevalieri

Abstract

A large body of fungal secondary metabolites has been discovered to exhibit potent antibacterial activities with distinctive mechanisms and has the potential to be an untapped resource for drug discovery. Here, we describe the isolation and characterization of five new antibacterial indole diketopiperazine alkaloids, namely 24,25-dihydroxyvariecolorin G (1), 25-hydroxyrubrumazine B (2), 22-chloro-25-hydroxyrubrumazine B (3), 25-hydroxyvariecolorin F (4), and 27-epi-aspechinulin D (5), along with the known analogue neoechinulin B (6) from a fungal strain of deep-sea cold seep-derived Aspergillus chevalieri. Among these compounds, 3 and 4 represented a class of infrequently occurring fungal chlorinated natural products. Compounds 1–6 showed inhibitory activities against several pathogenic bacteria with MIC values ranging from 4 to 32 μg/mL. It was revealed that compound 6 could induce structural damage to the Aeromonas hydrophila cells based on the observation by scanning electron microscopy (SEM), which led to the bacteriolysis and death of A. hydrophila, suggesting that neoechinulin B (6) might be a potential alternative to novel antibiotics development.

Peptides from Marine-Derived Fungi: Chemistry and Biological Activities

“…Moreover, the relative configurations obtained by an analysis of the 13 C chemical shift values and NOESY correlations of the key protons of the acetonide of 182 were in agreement with those obtained from DP4+ probability analysis. Thus, the absolute configurations of C-22 and C-23 were tentatively assigned as 22S,23R by correlating with the absolute configuration of C-12 which was unambiguously established as 12S [96].…”

“…A chemical investigation of a marine-derived fungus, Ascotricha sp. ZJ-M-5, furni cyclo-(Pro-Ala) (95), cyclo-(Ile-Leu) (96), and cyclo-(Gly-Pro) (97) (Figure 14), in additi 89 and 90 [69].…”

“…The Z geometry of the double bond at C-8 was established based on the downfield chemical shift of H-8 caused by the deshielding effect of the carbonyl group. The absolute configuration of Ala was determined as L by chiral HPLC of the hydrolysis products of 178-182 [96].…”

“…Given the significant antibacterial activity of 175 against A. hydrophilia (MIC = 4 µg/mL), a further antibacterial mechanism was assessed using scanning electron microscope (SEM) before and after treatment with 175. In addition to obvious cell deformation and serious damage to the cell membrane, 175 also caused deep grooves and clear pores on the bacterial surface leading to sufficient bacteriolysis and death of A. hydrophilia [96].…”

A Survey of Recently Discovered Naturally Occurring Organohalogen Compounds

“…The two new indole alkaloids 156 and 157 are found in the fungus Aspergillus chevalieri CS-122, which was isolated from a deep-sea cold seep sediment in the South China Sea. The former metabolite is active toward Vibrio harveyi (MIC 8 μg/mL; chloramphenicol, 2 μg/mL) . The cold-seep-derived fungus Cladosporium cladosporioides 8-1 yields the dimeric naphtha-γ-pyrone, 6-iodofonsecinone A ( 158 ), which is assigned the as configuration by comparison of its ECD spectrum with that of ( as )-fonsecinone A. Metabolite 158 is quite active against the marine microalga Prorocentrum minimum (IC 50 0.61 μg/mL) .…”