Neuronal Modulators from the Coral-Associated Fungi Aspergillus candidus

Abstract

Three new p-terphenyl derivatives, named 4″-O-methyl-prenylterphenyllin B (1) and phenylcandilide A and B (17 and 18), and three new indole-diterpene alkaloids, asperindoles E–G (22-24), were isolated together with eighteen known analogues from the fungi Aspergillus candidus associated with the South China Sea gorgonian Junceela fragillis. The structures and absolute configurations of the new compounds were elucidated on the basis of spectroscopic analysis, and DFT/NMR and TDDFT/ECD calculations. In a primary cultured cortical neuronal network, the compounds 6, 9, 14, 17, 18 and 24 modulated spontaneous Ca2+ oscillations and 4-aminopyridine hyperexcited neuronal activity. A preliminary structure–activity relationship was discussed.

Marine natural products

“…Norditerpene 291 and indone 292 were isolated from Aspergillus aculeatinus , 140 A. austroafricanus yielded prenylated indole alkaloids 293 and 294 and pteridine alkaloids 295 and 296 , the latter of which was obtained for the first time as a MNP. 141 Various A. candidus strains yielded p -terphenyls 297 , 142 298–300 143 and indole-diterpene alkaloids 301–303 , 143 304–307 . 144 Other Aspergillus strains were the source of viomellein derivatives 308 and 309 , 145 polyketides 310 and 311 (the latter a known synthetic derivative but new NP), 146 prenylated phenylbutyrolactones 312–315 , 147 phomaligol derivatives 316–319 , 148 320 and 321 , 149 and highly rearranged ergostanes 322 and 323 .…”

A Survey of Recently Discovered Naturally Occurring Organohalogen Compounds

“…25 A collection of the Bahamian sponge Aiolochroia crassa (previously, Pseudoceratina crassa) led to the discovery of nine new bromotyrosine alkaloids. These are debromoianthelline (60), pseudoceratinic acid (61), methyl pseudoceratinate (62), 13-oxo-ianthelline (63) Two other rare alkaloids are ma'edamines E (75) and F (76), which embrace a 1,2,3,5-tetrasubstituted pyridinium moiety and are found in Suberea sp. sponge from Olinawa.…”

“…Asperindole G (154) inhibits spontaneous Ca 2+ oscillations (SCOs), which play a crucial role in neuron development (EC 50 5.62 μM, amplitude; and EC 50 4.77 μM, frequency). 63 A strain of the fungus Aspergillus sydowii from a deep-sea (−1146 m) cold seep sediment from Taiwan yielded the new 7S-4-iodoflavilane (155). 64 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 fungus Aspergillus candidus , which is associated with the South China Sea gorgonian Junceella fragillis , produces the two new chlorinated asperindoles F ( 153 ) and G ( 154 ), along with a nonchlorinated analogue, some known analogues, and several p -terphenyls. Asperindole G ( 154 ) inhibits spontaneous Ca 2+ oscillations (SCOs), which play a crucial role in neuron development (EC 50 5.62 μM, amplitude; and EC 50 4.77 μM, frequency) …”

Methods and Strategies to Uncover Coral-Associated Microbial Dark Matter

“…Coral-associated fungi are also important producers of bioproducts with many biotechnological implications. For example, they can synthesize polyketides with antibacterial and antifouling activity ( 149 , 150 ), different bioactive peptides ( 151 , 152 ), terpenoids ( 153 , 154 ), and even neuronal modulators ( 153 , 155 ), among other secondary metabolites. Furthermore, coral fungal diversity can be utilized in water bioremediation because of its ability to degrade contaminants.…”