Targeted Isolation of Two New Anti-inflammatory and UV-A Protective Dipyrroloquinones from the Sponge-associated Fungus Aspergillus tamarii MCCF102

Abstract

In following up on observed in vitro anti-inflammatory activity of the organic extract of the marine sponge-derived fungus Aspergillus tamarii MCCF102, two new dipyrrolobenzoquinones, terreusinone B and C (1 and 2), were discovered along with the known analogue, terreusinone (3). The structures of 1–3 were determined by spectroscopic and spectrometric analyses, along with chemical inter-conversion. In vitro testing on lipopolysaccharide (LPS) stimulated RAW 264.7 murine macrophage cells revealed that 1–3 exhibit anti-inflammatory activity by inhibiting nitric oxide production in a dose-dependent manner (IC50 < 1 μM) without any cytotoxicity observed at the same concentrations. Due to this and the UV-A absorptive properties imparted by the highly conjugated structures of these molecules, the potential for using <b>1</b>–<b>3</b> or related analogues as natural sunscreen components is suggested. Gene sequencing and informatics biosynthetic gene cluster comparisons were insufficient to confidently elucidate the biosynthetic origins of these compounds, possibly suggesting the occurrence of a gene cluster not detected in the initial sequencing or a non-canonical pathway that should be further investigated.

Secondary Metabolites From the Grasshopper-Derived Entomopathogenic Fungus Aspergillus Tamarii NL3 and Their Biological Activities

“…Five known compounds, griseofulvin (1), isogriseofulvin (2), cytochalasin J (3), solamargine (4), and solasonine (5), were purified from the ethyl acetate portion of the culture broth of the entomopathogenic fungus A tamarii NL3. Except for solasonine (5), the isolated compounds are reported for the first time in the Aspergillus genus. Griseofulvin (1) and isogriseofulvin (2) exhibited antifungal effects against the reference fungi with MICs of 16 to 128 µg/mL, while cytochalasin J (3) inhibited B subtilis and A niger with MICs of 64 µg/mL.…”

“…2 The genus Aspergillus is rich in alkaloids, terpenes, steroids, and polyketones. 3 Aspergillus tamarii has produced structurally diverse compounds with a wide range of bioactivities, including an antibacterial pentacyclic indole alkaloid, 4 anti-inflammatory dipyrrolobenzoquinones, 5 antibiotic and cytotoxic cyclic peptides, 6 butenolides, 7 and anti-phytopathogenic indolyl diketopiperazines. 8 In a continuing search for new antimicrobial and antioxidant agents, we report herein the isolation and structural determination of 5 secondary metabolites from the ethyl acetate (EtOAc) extract of the entomopathogenic fungus A tamarii NL3 culture broth.…”

Marine natural products

“…151 Aspergillus strains derived from deep-sea sediment yielded a variety of metabolites including phenols 355 , 356 (C-8 epimers), 357 , 358 , 152 aromatic polyketides 359 – 361 and isoquinoline alkaloids 362 , 363 , 153 364 – 377 , 154 acremolin alkaloid 378 , 155 and cyclopropane acids 379 – 382 . 156 Sponge-derived strains were the source of 2,5-diketopiperazines 383 – 385 , 157 isocoumarin 386 , propylpyridinium anthraquinone 387 , resorcinol derivative 388 , 158 and dipyrroloquinones 389 , 390 , 159 whilst notoamide alkaloids 391 – 396 , 160 prenylated notoamide-type alkaloids 397 – 406 , 161 butenolides 407 – 411 and p -hydroxybenzaldehyde derivative 412 (ref. 162) were obtained from gorgonian-derived strains.…”

New Dipyrroloquinones from a Plant-Derived Endophytic Fungus Talaromyces sp.

“…Dipyrroloquinones are unusual alkaloids in nature, whose basic skeleton possesses a highly symmetrical pyrrole-benzoquinone-pyrrole tricyclic system [1]. Currently reported dipyrroloquinones have three types of structures, including terreusinones, zyzzyanones, and tsitsikammamines, and these analogues are mainly from marine sponges and fungi [2][3][4][5]. These compounds are biosynthetically derived from seco-pyrroloiminoquinones such as makaluvamines and discorhabdins [6].…”