A New Meroditerpene and a New Tryptoquivaline Analog from the Algicolous Fungus Neosartorya takakii KUFC 7898.

A new meroditerpene sartorenol (1), a new natural product takakiamide (2) and a new tryptoquivaline analog (3) were isolated, together with nine known compounds, including aszonapyrone A, chevalone B, aszonalenin, acetylaszonalenin, 3'-(4-oxoquinazolin-3-yl) spiro[1H-indole-3,5'-oxolane]-2,2'-dione, tryptoquivalines L, F and H, and the isocoumarin derivative, 6-hydroxymellein, from the ethyl acetate extract of the culture of the algicolous fungus Neosartorya takakii KUFC 7898. The structures of the new compounds were established based on 1D and 2D NMR spectral analysis, and, in the case of sartorenol (1) and tryptoquivaline U (3), X-ray analysis was used to confirm their structures and to determine the absolute configuration of their stereogenic carbons. Compounds 1, 2 and 3 were evaluated for their antimicrobial activity against Gram-positive and Gram-negative bacteria, and multidrug-resistant isolates from the environment; however, none exhibited antibacterial activity (MIC ˃ 256 mg/mL). The three new compounds did not show any quorum sensing inhibition in the screening protocol based on the pigment production by Chromobacterium violaceum (ATCC 31532).

Antibacterial and antibiofilm activities of tryptoquivalines and meroditerpenes isolated from the marine-derived fungi Neosartorya paulistensis, N. laciniosa, N. tsunodae, and the soil fungi N. fischeri and N. siamensis.

A new meroditerpene, sartorypyrone C (5), was isolated, together with the known tryptoquivalines L (1a), H (1b), F (1c), 3'-(4-oxoquinazolin-3-yl) spiro [1H-indole-3,5']-2,2'-dione (2) and 4(3H)-quinazolinone (3), from the culture of the marine sponge-associated fungus Neosartorya paulistensis (KUFC 7897), while reexamination of the fractions remaining from a previous study of the culture of the diseased coral-derived fungus N. laciniosa (KUFC 7896) led to isolation of a new tryptoquivaline derivative tryptoquivaline T (1d). Compounds 1a-d, 2, 3, and 5, together with aszonapyrones A (4a) and B (4b), chevalones B (6) and C (7a), sartorypyrones B (7b) and A (8), were tested for their antibacterial activity against four reference strains (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa), as well as the environmental multidrug-resistant isolates. Only aszonapyrone A (4a) and sartorypyrone A (8) exhibited significant antibacterial activity as well as synergism with antibiotics against the Gram-positive multidrug-resistant strains. Antibiofilm assays of aszonapyrone A (4a) and sartorypyrone A (8) showed that practically no biofilm was formed in the presence of their 2× MIC and MIC. However, the presence of a sub-inhibitory concentration of ½ MIC of 4a and 8 was found to increase the biofilm production in both reference strain and the multidrug-resistant isolates of S. aureus.

Thermal shift assays of marine-derived fungal metabolites from Aspergillus fischeri MMERU 23 against Leishmania major pteridine reductase 1 and molecular dynamics studies.

Marine-derived fungi are a promising source of bioactive molecules, especially species from extreme habitats. Although several secondary metabolites such as meroterpenoids and alkaloids have been isolated from cultures of Aspergillus fischeri, obtained from terrestrial habitats, there is no report on compounds isolated from marine-derived strains. Many metabolites isolated from marine-derived fungi exhibited a myriad of biological activities. Marine natural products have shown to be an important source of bioactive compounds and can assist in the discovery of molecules with affinity against validated targets from exclusive strains of parasites of medical importance such as pteridine reductase 1 (PTR1), from Leishmania major, which is essential for cell growth. Leishmaniasis is responsible for approximately 65,000 annual deaths. Despite the mortality data, drugs available for the treatment of patients are insufficient and have moderate therapeutic efficacy in addition to serious adverse effects, which make the development of new drugs urgent. The previously described aszonalenin (ASL), aszonapyrone A (ASP), acetylaszonalenin (ACZ), and helvolic acid (HAC) were isolated from the ethyl acetate extract of the culture of a marine sponge-associated A. fischeri MMERU 23 and their affinities against PTR1 were determined by ThermoFluor®. Among the tested compounds, only ACZ showed dose-dependent affinity against PTR1. Moreover, complementary molecular dynamics studies (t = 100 000 ps) have showed that this molecule performs hydrogen bonds with key residues at the active site for more than 60% of the productive trajectory time. The results indicate that ACZ could be a promising PTR1 inhibitor and a potential candidate for development of antileishmanial drug.Communicated by Ramaswamy H. Sarma.