Scalarane-Type Sesterterpenoids from the Marine Sponge Lendenfeldia sp. Alleviate Inflammation in Human Neutrophils

Sponge-derived scalaranes are remarkable sesterterpenoids previously found to exhibit profound inhibitory effects against neutrophilic inflammation. In our current work, we constructed the metabolomic profile of marine sponge Lendenfeldia sp. for the first time using a tandem mass spectrometry (MS/MS) molecular networking approach. The results highlighted the rich chemical diversity of these scalaranes, motivating us to conduct further research to discover novel scalaranes targeting neutrophilic inflammation. MS- and NMR-assisted isolation and elucidation led to the discovery of seven new homoscalaranes, lendenfeldaranes K–Q (1–7), characterized by methylation at C-24, together with five known derivatives, lendenfeldarane B (8), 25-nor-24-methyl-12,24-dioxoscalar-16-en-22-oic acid (9), 24-methyl-12,24,25-trioxoscalar-16-en-22-oic acid (10), felixin B (11), and 23-hydroxy-20-methyldeoxoscalarin (12). Scalaranes 1–4 and 6–12 were assayed against superoxide anion generation and elastase release, which represented the neutrophilic inflammatory responses of respiratory burst and degranulation, respectively. The results indicated that 1–3 and 6–12 exhibited potential anti-inflammatory activities (IC50 for superoxide anion scavenging: 0.87~6.57 μM; IC50 for elastase release: 1.12~6.97 μM).

[1]  P. Sung,et al.  Sponge-Derived 24-Homoscalaranes as Potent Anti-Inflammatory Agents , 2020, Marine drugs.

[2]  H. Hsieh,et al.  Lophatherum gracile Brongn. attenuates neutrophilic inflammation through inhibition of JNK and calcium. , 2020, Journal of ethnopharmacology.

[3]  P. Sung,et al.  Probing Anti-Proliferative 24-Homoscalaranes from a Sponge Lendenfeldia sp. , 2020, Marine drugs.

[4]  S. Sung,et al.  Molecular Networking Reveals the Chemical Diversity of Selaginellin Derivatives, Natural Phosphodiesterase-4 Inhibitors from Selaginella tamariscina. , 2019, Journal of natural products.

[5]  O. Kvalheim,et al.  Integration of Biochemometrics and Molecular Networking to Identify Antimicrobials in Angelica keiskei , 2018, Planta Medica.

[6]  R. Sakai,et al.  Two New Mycosporine-like Amino Acids LC-343 and Mycosporine-ethanolamine from the Micronesian Marine Sponge Lendenfeldia chondrodes , 2017 .

[7]  Jonathan Bisson,et al.  Integration of Molecular Networking and In-Silico MS/MS Fragmentation for Natural Products Dereplication. , 2016, Analytical chemistry.

[8]  Li-Hsueh Wang,et al.  New Scalarane Sesterterpenoids from the Formosan Sponge Ircinia felix , 2015, Marine drugs.

[9]  M. Jacob,et al.  Polybrominated diphenyl ethers from the marine organisms Lendenfeldia dendyi and Sinularia dura with anti-MRSa activity , 2015, Medicinal Chemistry Research.

[10]  Nuno Bandeira,et al.  Mass spectral molecular networking of living microbial colonies , 2012, Proceedings of the National Academy of Sciences.

[11]  Qianjia Yuan,et al.  Synthesis of the scalarane sesterterpenoid 16-deacetoxy-12-epi-scalarafuranacetate. , 2011, The Journal of organic chemistry.

[12]  Miguel A. González.  Scalarane Sesterterpenoids , 2010 .

[13]  Yang Liu,et al.  Molecular-targeted antitumor agents. 19. Furospongolide from a marine Lendenfeldia sp. sponge inhibits hypoxia-inducible factor-1 activation in breast tumor cells. , 2008, Journal of natural products.

[14]  D. Nagle,et al.  Cytotoxic metabolites from an Indonesian sponge Lendenfeldia sp. , 2007, Journal of natural products.

[15]  S. Ross,et al.  Two New Sulfated Sterols from the Marine Sponge Lendenfeldia dendyi , 2007 .

[16]  R. Sakai,et al.  1-Deoxynojirimycin Derivatives from the Marine Sponge Lendenfeldia chondrodes , 2006, The Journal of Antibiotics.

[17]  L. Marabini,et al.  Anti-Inflammatory Activity of Thymol: Inhibitory Effect on the Release of Human Neutrophil Elastase , 2006, Pharmacology.

[18]  A. Hizi,et al.  New sesterterpenes from Madagascan Lendenfeldia sponges , 2004 .

[19]  R. Ebel,et al.  Employing dereplication and gradient 1D NMR methods to rapidly characterize sponge-derived sesterterpenes. , 2002, Journal of natural products.

[20]  G. Bernardinelli,et al.  Absolute structure and absolute configuration. , 1999, Acta crystallographica. Section A, Foundations of crystallography.

[21]  Sera,et al.  A new epidioxy sterol as an antifouling substance from a palauan marine sponge, lendenfeldia chondrodes , 1999, Journal of natural products.

[22]  P. Crews,et al.  Homoscalarane sesterterpenes from Lendenfeldia frondosa. , 1992, Journal of natural products.

[23]  M. Endo,et al.  Pharmacologically active homosesterterpenes from palauan sponges , 1987 .

[24]  J. Clardy,et al.  Metabolites of the dorid nudibranch Chromodoris sedna , 1983 .

[25]  R. Wells,et al.  Five new C26 tetracyclic terpenes from a sponge (Lendenfeldia sp.) , 1982 .