Research topic: Marine natural products as potential drug leads

Dr. LI Xu-Wen is now a professor of marine natural product chemistry at Shanghai Institute of Materia Medica, Chinese Academy of Sciences. His research interests cover chemical ecology guided discovery, biomimetic synthesis, and function-oriented synthesis of new and bioactive marine natural products toward new drug leads. In the past five years, he has published over 40 peer-reviewed articles as a corresponding author including Angew Chem Int Ed, J Med Chem, Org Lett, Acta Pharm Sin B, J Org Chem, etc. He won the 22th “China Pharmaceutical Association-Servier Young Medicinal Chemistry Award” in 2019.

Title:Chemical ecology-driven discovery of bioactive marine natural products as potential drug leads
[Abstract] In this special issue, we are please to publish four original articles on MNPs, which represent the currently most studied marine living organisms, soft corals, sponges, and marine derived fungi, from far sea, deep sea or special mangrove living conditions. The issue begins with the paper reported the discovery of new lobane type diterpenoids from a soft coral Sinularia polydactyla off Xisha island, away from continental shelf, by our group. This is an extended work by Guo YW and co-workers, by studying the living environment influenced variation of MNPs, which proved that the same species in different sea area could produce diterpenoids of different skeletons, exemplified by the reported new lobanes and the previous reported new skeletons xishacorenes. The second paper is the study of another popularly investigated marine animals, the sponges, which were also collected of the far sea, Xisha area. In this paper, a series of new and interesting polyhydroxylated steroids were discovered and characterized by Li GQ et al.. The polyhydroxylated nature of these steroids may also related to the living circumstance of the sponge Plakortis sp. The third and fourth paper both reported the marine fungi derived molecules. Li DH et al. reported the new cytotoxic mycophenolic acid derivatives from the deep-sea sediment-derived fungus Penicillium parvum HDN17-478, whereas Long YH et al. described the new anti-microbial polyketides from the mangrove endophytic fungus Aspergillus sp. 085242.

Title:New lobane-type diterpenoids from the Xisha soft coral Sinularia polydactyla
[Abstract] Lobane-type diterpenoids are not frequently discovered from marine soft corals. In this paper, three new lobane type diterpenes, 13-methoxyloba-8,10,15(16),17(18)-tetraene ( 1 ), 8,10,13(15)Z,16E-lobatetraene ( 2 ) and 19-hydroxy-lobatetraene ( 3 ), and a new natural compound, 17,18-epoxyloba-16-acetoxy-8,10,13(15)-trien ( 4 ), co-occurring with a known related diterpenoid, 18-methoxyloba-8,10,13(15),16(17)-tetraene ( 5 ), were isolated from the South China Sea soft coral Sinularia polydactyla. The structures of new compounds were determined by extensive spectroscopic analysis and by comparison with those reported in the literature. In bioassay, all the isolates were inactive on antibacterial, PTP1B inhibitory, and immunological activities. This study increased the chemical diversity of marine diterpenoids.

Title:Four new polyhydroxylated steroids from the South Sea sponge Plakortis sp.
[Abstract] Four new polyhydroxylated steroids plaksterols A–D ( 1 – 4 ), together with two known related steroids ergost-7,9(11),22-trien-3β,5α,6α-triol ( 5 ) and ergosta-6β-methoxy-7,22-diene-3β,5α-diol ( 6 ), were isolated from methanol extract of the South China Sea marine sponge Plakortis sp. Their structures were identified by spectroscopic analysis, including NMR, MS, and IR. The cytotoxicity of the polyhydroxylated steroids were evaluated, and compound 6 showed moderate inhibitory activities against K562, HL-60 and BEL-7402 cells.

Title:Penicacids E−G, three new mycophenolic acid derivatives from the marine-derived fungus Penicillium parvum HDN17-478
[Abstract] Three new mycophenolic acid derivatives, penicacids E−G ( 1 − 3 ), together with three known analogues, mycophenolic acid ( 4 ), 4′-hydroxy-mycophenolic acid ( 5 ) and mycophenolic methyl ester ( 6 ), were isolated from a marine-derived fungus Penicillium parvum HDN17-478 from a South China Sea marine sediment sample. The structures of compounds 1 − 3 were elucidated by HRMS, NMR, and Mosher’s method. Among them, compounds 1 and 2 were the first examples of mycophenolic acid analogs with a double bond at C-3′/C-4′ position. The cytotoxicity of 1 − 6 was evaluated against the HCT-116, BEL-7402, MGC-803, SH-SY5Y, HO-8910 and HL-60 cell lines, and compounds 4 and 6 showed potent cytotoxicity with IC50 values ranging from 1.69 to 12.98 μmol·L–1.

Title:New furo[3,2-h]isochroman from the mangrove endophytic fungus Aspergillus sp. 085242
[Abstract] Four new compounds, asperisocoumarin G ( 1 ), asperisocoumarin H ( 2 ), (±)-asperisocoumarin I [(±)- 3 ], along with the known pergillin ( 4 ) and penicisochroman L ( 5 ) were isolated from a mangrove endophytic fungus Aspergillus sp. 085242 by further chemical investigation. The structures of the new compounds, including their absolute configurations, were established by analysis of HR-ESI-MS and NMR spectroscopic data, and ECD calculation. Asperisocoumarins G-I ( 1 − 3 ) were new isocoumarins belonging to the class of furo[3, 2-h]isocoumarins which are rarely found in natural sources. All of the isolated compounds were evaluated for their α-glucosidase inhibitory effects, and compounds 1 and 4 showed moderate α-glucosidase inhibitory activity, respectively. In an antimicrobial test, the racemate of 3 showed antibacterial activity against Salmonella.