Bioactive 3-Decalinoyltetramic Acids Derivatives From a Marine-Derived Strain of the Fungus Fusarium equiseti D39

Abstract

Two novel 3-decalinoyltetramic acid (3DTA) derivatives, namely fusarisetins C and D ( 1 and 2 ), and four known derivatives ( 3–6 ) were isolated from the marine-derived fungus Fusarium equiseti D39. Their structures were determined by spectroscopic data, vibrational circular dichroism (VCD) calculations, and X-ray crystallography. Compound 2 was identified as the first fusarisetin to possess an unprecedented carbon skeleton with a tetracyclic ring system comprised of a decalin moiety (6/6) and a tetramic acid moiety. A plausible biosynthetic pathway for the isolated compounds was proposed. All 3DTAs derivatives exhibited a potent phytotoxicity, and 5 also displayed a remarkable anti-phytopathogenic activity superior to the positive control resulting in damage of the cell membrane of Pseudomonas syringae and ensuing leakage of the intracellular components. Here, the phytotoxicity of fusarisetins has been reported for the first time. The OSMAC fermentation optimization approach to give 5 was performed by varying the culture media and salinities. The results showed that potato liquid medium with 1% salinity is the most favorable condition for the production of 5 .

Pyrenosetin D, a New Pentacyclic Decalinoyltetramic Acid Derivative from the Algicolous Fungus Pyrenochaetopsis sp. FVE-087

“…The 'decalin' moiety is a common structural motif in an array of marine fungal natural products [13,32,33]. It has been proposed that the decalin ring serves as a primary ring system or a scaffold to form polycyclic metabolites, with bicyclic decalins being the most common [11,13,[32][33][34][35]. The chemical investigation of the marine sponge-derived fungus Trichoderma harzianum in 1993 led to the isolation of the first bicyclic decalin derivative trichoharzin isolated from a marine fungus.…”

The Biological and Chemical Diversity of Tetramic Acid Compounds from Marine-Derived Microorganisms

“…These two molecules were also later isolated from the marine-derived fungi Fusarium sp. 152 and F. equiseti D39 [47] and displayed potent anti-phytopathogenic bacterial and fungal activities [47]. Notably, equisetin (40) exhibited potent anti-methicillin-resistant Staphylococcus aureus (MRSA) activity (MIC = 1 µg/mL, equivalent to vancomycin) and antimicrobial activities against Pseudomonas syringae and Rhizoctonia cerealis (MIC = 1.1 and 8.4 µM, respectively) superior to the positive control and could be exploited as a potential antimicrobial drug candidate [48].…”

“…yielded sch210972 (46), which could inhibit human leucocyte elastase (HLE), with an IC 50 value of 1.04 µg/mL, and revealed moderate inhibition of the growth of Bacillus megaterium [51]; 46 can also be considered a chemokine receptor CCR-5 inhibitor, with an IC 50 of 79 nM [52]. Another marine-sponge-derived fungus, Beauveria bassiana, afforded a 3-DTA named beauversetin (47), which exhibited moderate cytotoxicity against a panel of six cell lines, with a mean IC 50 = 3.09 µg/mL for a monolayer assay, but it was devoid of antimicrobial activity [51]. A class of new 3-DTAs, trichobotrysins A-E (48-52), were discovered from the culture of a deep-sea-derived fungus Trichobotrys effuse DFFSCS021 [53].…”

“…These isolated compounds 66-70 had moderate or potent cytotoxicity against three leukemia HTCLs (IC 50 = 6.1-61 µM), two of which, 69 and 70, bear a diene moiety (C-6 to C-8) and exhibited significant cytotoxicity against HL-60, with IC 50 values of 6.1 and 6.2 µM, respectively, similar to that of 5-fluorouracil (IC 50 = 4.5 µM) [62]. Using the bioassay-LCMS-1 H NMR-screening technology, four 3-DTA derivatives, namely fusarisetins A-D (71-74), were discovered from a marine-derived fungus Fusarium equiseti D39 and displayed phytotoxicity [47]. Interesting, fusarisetins A-C possess a rare carbon skeleton with a 6/6/5/5/5 pentacyclic ring system, while fusarisetin D is the first-discovered fusarisetin with an unusual 6/6/5/5 tetracyclic ring framework.…”

“…Chemical structures of 3-decalinoyltetramic acids(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53).…”