New Cyclotetrapeptides and a New Diketopiperzine Derivative from the Marine Sponge-Associated Fungus Neosartorya glabra KUFA 0702

Abstract

Two new cyclotetrapeptides, sartoryglabramides A (5) and B (6), and a new analog of fellutanine A (8) were isolated, together with six known compounds including ergosta-4, 6, 8 (14), 22-tetraen-3-one, ergosterol 5, 8-endoperoxide, helvolic acid, aszonalenin (1), (3R)-3-(1H-indol-3-ylmethyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione (2), takakiamide (3), (11aR)-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H,11aH)-dione (4), and fellutanine A (7), from the ethyl acetate extract of the culture of the marine sponge-associated fungus Neosartorya glabra KUFA 0702. The structures of the new compounds were established based on extensive 1D and 2D spectral analysis. X-ray analysis was also used to confirm the relative configuration of the amino acid constituents of sartoryglabramide A (5), and the absolute stereochemistry of the amino acid constituents of sartoryglabramide A (5) and sartoryglabramides B (6) was determined by chiral HPLC analysis of their hydrolysates by co-injection with the d- and l- amino acids standards. Compounds 1–8 were tested for their antibacterial activity against Gram-positive (Escherichia coli ATCC 25922) and Gram-negative (Staphyllococus aureus ATCC 25923) bacteria, as well as for their antifungal activity against filamentous (Aspergillus fumigatus ATCC 46645), dermatophyte (Trichophyton rubrum ATCC FF5) and yeast (Candida albicans ATCC 10231). None of the tested compounds exhibited either antibacterial (MIC > 256 μg/mL) or antifungal activities (MIC > 512 μg/mL).

A New Dihydrochromone Dimer and Other Secondary Metabolites from Cultures of the Marine Sponge-Associated Fungi Neosartorya fennelliae KUFA 0811 and Neosartorya tsunodae KUFC 9213

“…The structures of byssochlamic acid [ 7 ], hopan-3β,22-diol ( 5 ) [ 15 ], chevalone B [ 12 ], chevalone C [ 16 ], sartorypyrone B [ 5 ], helvolic acid [ 5 ], lumichrome ( 6 ) [ 21 ], harmane ( 7 ) [ 20 ], β-sitostenone [ 8 ], ergosta-4,6,8 [ 14 ] 22-tetraen-3-one [ 19 ], cyathisterone [ 10 ], dehydromevalonic acid lactone [ 6 ], aszonalenin [ 13 ], secalonic acid A [ 14 ] and fellutanine A [ 13 ] ( Figure 1 and Supplementary Materials, Figure S1 ) were elucidated by analysis of their 1 H, 13 C NMR spectra and HRMS data, as well as by comparison of their spectral data to those reported in the literature ( Supplementary Materials, Figures S2–S31 ).…”

“…Sfrs 316–365 were combined (35 mg) and purified by TLC (Silica gel G 254 , petrol-CHCl 3 -EtOAc-HCO 2 H, 1:8:1:0.01) to give 10.5 mg of chevalone B [ 12 ] and 4 mg of dankasterone A ( 2 ). Sfrs 418–480 were combined (11.3 mg) and crystallized in MeOH to give 7 mg of aszonalenin [ 13 ] Fr 449 (736 mg) was crystallized in MeOH to give 138 mg of secalonic acid A [ 14 ]. Frs 450–452 were combined (1.7 g) and applied on a column of silica gel (100 g), and eluted with mixtures of petrol-CHCl 3 andCHCl 3 -Me 2 CO, wherein 250 mL sfrs were collected as follows: Sfrs 1–23 (petrol-CHCl 3 , 1:1), 24–58 (petrol-CHCl 3 , 3:7), 59–150 (petrol-CHCl 3 , 1:9), 151–594 (CHCl 3 ), 595–649 (CHCl 3 -Me 2 CO, 19:1), 650–735 (CHCl 3 -Me 2 CO, 9:1), 736–955 (CHCl 3 -Me 2 CO, 9:1).…”

“…Frs 617–623 were combined (39 mg) and applied on a column of Sephadex LH-20 (10 g) and eluted with a 1:1 mixture of MeOH: CH 2 Cl 2 , wherein 30 sfrs of 3 mL were collected. Sfrs 17–30 were combined and crystalized in MeOH to give 4.5 mg of fellutanine A [ 13 ]. Frs 631–675 were combined (3.61 g) and crystallized in MeOH to give further 68.3 mg of secalonic acid A.…”

“…Chromatographic fractionation and further purification of the ethyl acetate extract of N. fennelliae KUFA 0811, yielded a previously undescribed 2,3-dihydro-4 H -chromen-4-one dimer which we have named paecilin E ( 1 ), in addition to the previously described dehydromevalonic acid lactone [ 6 ], byssochlamic acid [ 7 ], β-sitostenone [ 8 ], ergosta-4,6,8 (14), 22-tetraen-3-one [ 9 ], cyathisterone [ 10 ], dankasterone A ( 2 ) [ 11 ], chevalone B [ 12 ], helvolic acid [ 5 ], aszonalenin [ 13 ], secalonic acid A [ 14 ] and fellutanine A [ 13 ]. The ethyl acetate extract of N. tsunodae KUFC 9213 furnished, besides sartorypyrone B and helvolic acid which were previous isolated in our first study [ 5 ], byssochlamic acid [ 7 ], hopan-3β,22-diol ( 5 ) [ 15 ], chevalone C [ 16 ], a chromanol derivative ( 3 ) [ 17 , 18 ], (3β,5α,22 E )-3,5-dihydroxyergosta-7,22-dien-6-one ( 4 ) [ 19 ], the alkaloid harmane ( 7 ) [ 20 ], and lumichrome ( 6 ) [ 21 ].…”

Natural Cyclic Peptides as an Attractive Modality for Therapeutics: A Mini Review

“…isolate which was found in marine sediment collected from the intertidal zone of Frobisher Bay, Nunavut, Canada. None of these compounds exhibited antimicrobial or cytoxic activities [ 100 ].…”