title: Anti-Chikungunya viral activities of aplysiatoxin-related compounds from the marine cyanobacterium Trichodesmium erythraeum.
abstract: Tropical filamentous marine cyanobacteria have emerged as a viable source of novel bioactive natural products for drug discovery and development. In the present study, aplysiatoxin (1), debromoaplysiatoxin (2) and anhydrodebromoaplysiatoxin (3), as well as two new analogues, 3-methoxyaplysiatoxin (4) and 3-methoxydebromoaplysiatoxin (5), are reported for the first time from the marine cyanobacterium Trichodesmium erythraeum. The identification of the bloom-forming cyanobacterial strain was confirmed based on phylogenetic analysis of its 16S rRNA sequences. Structural determination of the new analogues was achieved by extensive NMR spectroscopic analysis and comparison with NMR spectral data of known compounds. In addition, the antiviral activities of these marine toxins were assessed using Chikungunya virus (CHIKV)-infected cells. Post-treatment experiments using the debrominated analogues, namely compounds 2, 3 and 5, displayed dose-dependent inhibition of CHIKV when tested at concentrations ranging from 0.1 µM to 10.0 µM. Furthermore, debromoaplysiatoxin (2) and 3-methoxydebromoaplysiatoxin (5) exhibited significant anti-CHIKV activities with EC50 values of 1.3 μM and 2.7 μM, respectively, and selectivity indices of 10.9 and 9.2, respectively.
authors.affiliation: Natural Sciences and Science Education, National Institute of Education, Nanyang Technological University, 1 Nanyang Walk, Singapore 637616, Singapore. deepak.k.july@gmail.com.
authors.forename: Deepak Kumar
authors.initials: DK
authors.lastname: Gupta
authors.affiliation: Natural Sciences and Science Education, National Institute of Education, Nanyang Technological University, 1 Nanyang Walk, Singapore 637616, Singapore. parveenk@nus.edu.sg.
authors.forename: Parveen
authors.initials: P
authors.lastname: Kaur
authors.affiliation: Natural Sciences and Science Education, National Institute of Education, Nanyang Technological University, 1 Nanyang Walk, Singapore 637616, Singapore. leongst1@gis.a-star.edu.sg.
authors.forename: See Ting
authors.initials: ST
authors.lastname: Leong
authors.affiliation: Natural Sciences and Science Education, National Institute of Education, Nanyang Technological University, 1 Nanyang Walk, Singapore 637616, Singapore. liktong.tan@nie.edu.sg.
authors.forename: Lik Tong
authors.initials: LT
authors.lastname: Tan
authors.affiliation: Natural Sciences and Science Education, National Institute of Education, Nanyang Technological University, 1 Nanyang Walk, Singapore 637616, Singapore. michele@waikato.ac.nz.
authors.forename: Michèle R
authors.initials: MR
authors.lastname: Prinsep
authors.affiliation: Natural Sciences and Science Education, National Institute of Education, Nanyang Technological University, 1 Nanyang Walk, Singapore 637616, Singapore. justin_chu@nuhs.edu.sg.
authors.forename: Justin Jang Hann
authors.initials: JJ
authors.lastname: Chu
mesh_terms: D000818:Animals; D000998:Antiviral Agents; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002646:Chikungunya virus / Q000187:drug effects*; D006224:Cricetinae; D000458:Cyanobacteria / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D005068:Eutrophication; D006801:Humans; D008235:Lyngbya Toxins / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D012336:RNA, Ribosomal, 16S / Q000096:biosynthesis; D010948:Viral Plaque Assay
chemical_list: D000998:Antiviral Agents; D008235:Lyngbya Toxins; D012336:RNA, Ribosomal, 16S; C006610:aplysiatoxin