Amoenucles A−F, novel nucleoside derivatives with TNF-α inhibitory activities from Aspergillus amoenus TJ507

Abstract

Amoenucles A−F (1−6), six previously undescribed nucleoside derivatives, and two known analogs (7 and 8) were isolated from the culture of Aspergillus amoenus TJ507. Their structures were elucidated through spectroscopic analysis, single-crystal X-ray crystallography, and chemical reactions. Notably, 3 and 4 represent the first reported instances of nucleosides with an attached pyrrole moiety. Of particular significance, the absolute configuration of the sugar moiety of 1−4 was determined using nuclear magnetic resonance (NMR), electric circular dichroism (ECD) calculations, and a hydrolysis reaction, presenting a potentially valuable method for confirming nucleoside structures. Furthermore, 1, 2, and 5−8 exhibited potential tumor necrosis factor α (TNF-α) inhibitory activities, which may provide a novel chemical template for the development of agents targeting autoimmune and inflammatory diseases.

Keywords

Aspergillus amoenus TJ507 / Nucleoside derivatives / Intramolecular transesterification / Tumor necrosis factor α (TNF-α)

References

[1] Chien M, Anderson TK, Jockusch S, et al. Nucleotide analogues as inhibitors of SARS-CoV-2 polymerase, a key drug target for COVID-19. J Proteome Res. 2020; 19(11):4690-4697. https://doi.org/10.1021/acs.jproteome.0c00392.

[2] Curtis BJ, Schwertfeger TJ, Burkhardt RN, et al. Oligonucleotide catabolism-derived gluconucleosides in caenorhabditis elegans. J Am Chem Soc. 2023; 145(21):11611-11621. https://doi.org/10.1021/jacs.3c01151.

[3] Jordheim LP, Durantel D, Zoulim F, et al. Advances in the development of nucleoside and nucleotide analogues for cancer and viral diseases. Nat Rev Drug Discov. 2013; 12(6):447-464. https://doi.org/10.1038/nrd4010.

[4] Shelton J, Lu X, Hollenbaugh JA, et al. Metabolism, biochemical actions, and chemical synthesis of anticancer nucleosides, nucleotides, and base analogs. Chem Rev. 2016; 116(23):14379-14455. https://doi.org/10.1021/acs.chemrev.6b00209.

[5] Abbas M, Elshahawi SI, Wang X, et al. Puromycins B-E, naturally occurring amino-nucleosides produced by the himalayan isolate Streptomyces sp. PU-14G. J Nat Prod. 2018; 81(11):2560-2566. https://doi.org/10.1021/acs.jnatprod.8b00720.

[6] Bracegirdle J, Gordon DP, Harvey JE, et al. Kinase-inhibitory nucleoside derivatives from the pacific bryozoan Nelliella nelliiformis. J Nat Prod. 2020; 83(2):547-551. https://doi.org/10.1021/acs.jnatprod.9b01231.

[7] Maffioli SI, Zhang Y, Degen D, et al. Antibacterial nucleoside-analog inhibitor of bacterial RNA polymerase. Cell. 2017; 169(7):1240-1248. https://doi.org/10.1016/j.cell.2017.05.042.

[8] Rossiter SE, Fletcher MH, Wuest WM. Natural products as platforms to overcome antibiotic resistance. Chem Rev. 2017; 117(19):12415-12474. https://doi.org/10.1021/acs.chemrev.7b00283.

[9] Zafrir IE, Torres MR, Prudhomme J, et al. Farnesides A and B, sesquiterpenoid nucleoside ehers from a marine-derived Streptomyces sp. strain CNT-372 from Fiji. J Nat Prod. 2013; 76(9):1815-1818. https://doi.org/10.1021/np400351t.

[10] Murakami R, Fujita Y, Kizuka M, et al. A-94964, a novel inhibitor of bacterial translocase I, produced by Streptomyces sp. SANK 60404. J Antibiot. 2008; 61(9):537-544. https://doi.org/10.1038/ja.2008.71.

[11] Robinson FA. Chemistry of penicillin. Analyst. 1947; 72(856):274-276. https://doi.org/10.1039/an9477200274.

[12] Evidente A, Kornienko A, Cimmino A, et al. Fungal metabolites with anticancer activity. Nat Prod Rep. 2014; 31(5):617-627. https://doi.org/10.1039/C3NP70078J.

[13] Xu QS, Zhu HJ, Sun ZQ, et al. Lysohexaenetides A and B, linear lipopeptides from Lysobacter sp. DSM.3655 identified by heterologous expression in Streptomyces. Chin J Nat Med. 2023; 21(6):454-458. https://doi.org/10.1016/S1875-5364(23)60473-X.

[14] Krukemyer JJ. Lovastatin: a new cholesterol-lowering agent. Pharmacotherapy. 1987; 7(6):198-210. https://doi.org/10.1002/j.1875-9114.1987.tb03524.x.

[15] Liu N, Song MN, Zhang QQ, et al. GKK1032B from endophytic Penicillium citrinum induces the apoptosis of human osteosarcoma MG63 cells through caspase pathway activation. Chin J Nat Med. 2022; 20(1):67-73. https://doi.org/10.1016/S1875-5364(21)60108-5.

[16] Salman K, Zhu H, Sun Z, et al. Seven drimane-type sesquiterpenoids from an earwig-associated Aspergillus sp. Chin J Nat Med. 2023; 21(1):58-64. https://doi.org/10.1016/S1875-5364(23)60385-1.

[17] Deng M, Chen X, Qiao Y, et al. Isolation, absolute configurations and bioactivities of pestaphilones A-I: undescribed methylated side chain containing-azaphilones from Pestalotiopsis oxyanthi. Phytochemistry. 2022;194:113045. https://doi.org/10.1016/j.phytochem.2021.113045.

[18] Hu H, Li Y, Shi Z, et al. Discovery of ergosterol derivative from Aspergillus sp. TJ507 that protects against hepatic ischemia/reperfusion injury. Bioorg Chem. 2023;135:106530. https://doi.org/10.1016/j.bioorg.2023.106530.

[19] Qi C, Bao J, Wang J, et al. Asperterpenes A and B, two unprecedented meroterpenoids from Aspergillus terreus with BACE1 inhibitory activities. Chem Sci. 2016; 7(10):6563-6572. https://doi.org/10.1039/C6SC02464E.

[20] Qiao Y, Xu Q, Feng W, et al. Asperpyridone A: an unusual pyridone alkaloid exerts hypoglycemic activity through the insulin signaling pathway. J Nat Prod. 2019; 82(10):2925-2930. https://doi.org/10.1021/acs.jnatprod.9b00188.

[21] Zhang Y, Zhao X, Cao Y, et al. Bioactive indole alkaloid from Aspergillus amoenus TJ507 that ameliorates hepatic ischemia/reperfusion injury. J Nat Prod. 2023; 86(8):2059-2064. https://doi.org/10.1021/acs.jnatprod.3c00251.

[22] Jiao P, Mudur SV, Gloer JB, et al. Kipukasins, nucleoside derivatives from Aspergillus versicolor. J Nat Prod. 2007; 70(8):1308-1311. https://doi.org/10.1021/np070241l.

[23] Sethi JK, Hotamisligil GS. Metabolic messengers: tumour necrosis factor. Nat Metab. 2021; 3(10):1302-1312. https://doi.org/10.1038/s42255-021-00470-z.

[24] Jang DI, Lee AH, Shin HY, et al. The role of tumor necrosis factor alpha (TNF-α) in autoimmune disease and current TNF-α inhibitors in therapeutics. Int J Mol Sci. 2021; 22(5):2719. https://doi.org/10.3390/ijms22052719.

[25] He MM, Smith AS, Oslob JD, et al. Small-molecule inhibition of TNF-α. Science. 2005; 310(5750):1022-1025. https://doi.org/10.1126/science.1116304.

[26] Javaid N, Patra MC, Cho DE, et al. An orally active, small-molecule TNF inhibitor that disrupts the homotrimerization interface improves inflammatory arthritis in mice. Sci Signal. 2022; 15(759):eabi8713. https://doi.org/10.1126/scisignal.abi8713.

[27] Lai X, Wei J, Ding X. Paeoniflorin antagonizes TNF-α-induced L929 fibroblastoma cells apoptosis by inhibiting NF-κB p65 activation. Dose Response. 2018; 16(2):1559325818774977. https://doi.org/10.1177/1559325818774977.

[28] Sun W, Wu Y, Zheng M, et al. Discovery of an orally active small-molecule tumor necrosis factor-α inhibitor. J Med Chem. 2020; 63(15):8146-8156. https://doi.org/10.1021/acs.jmedchem.0c00377.

[29] Sawai H. Induction of apoptosis in TNF-α treated L 929 cells in the presence of necrostatin-1. Int J Mol Sci. 2016; 17(10):1678. https://doi.org/10.3390/ijms17101678.

[30] Zang Y, Gong YH, Li XW, et al. Canescones A-E: aromatic polyketide dimers with PTP1B inhibitory activity from Penicillium canescens. Org Chem Front. 2019; 6(18):3274-3281. https://doi.org/10.1039/C9QO00820A.