title: Design, synthesis, and biological evaluation of crenatoside analogues as novel influenza neuraminidase inhibitors.
abstract: Natural products, especially derived from TCMH, have been found to exert antiviral effects against influenza virus. Crenatoside, a phenylethanoid glycoside from Pogostemon cablin Benth, which has been shown as a novel effective NA inhibitor previously, is considered as the leading compound for our further SARs studies. This work presented design, synthesis of novel crenatoside analogues from readily available d-Glucose and l-rhamnose in a convergent manner. Furthermore, their biological activities and SARs were also investigated. Especially, compound 2 h showed impressive IC50 = 27.77 μg/mL against NAs, which is 3 folds more potent than the leading compound crenatoside (IC50 = 89.81 μg/mL). These results would promise their therapeutic potential for influenza disease.
authors.affiliation: School of Pharmaceutical Sciences, Central South University, 172 Tongzipo Road, Yuelu District, Changsha 410013, PR China.
authors.forename: Bao-Long
authors.initials: BL
authors.lastname: Chen
authors.affiliation: Hunan University of Chinese Medicine, PR China.
authors.forename: Ya-Jing
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Central South University, 172 Tongzipo Road, Yuelu District, Changsha 410013, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Guo
authors.affiliation: School of Pharmaceutical Sciences, Central South University, 172 Tongzipo Road, Yuelu District, Changsha 410013, PR China. Electronic address: zenggy2013@csu.edu.cn.
authors.forename: Guang-Yao
authors.initials: GY
authors.lastname: Zeng
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D002109:Caffeic Acids / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D005960:Glucosides / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000201:enzymology; D009980:Influenza A virus / Q000187:drug effects / Q000201:enzymology*; D007251:Influenza, Human / Q000188:drug therapy / Q000821:virology; D008958:Models, Molecular; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D002109:Caffeic Acids; D004791:Enzyme Inhibitors; D005960:Glucosides; C083069:crenatoside; D009439:Neuraminidase
keywords: Crenatoside derivatives; Design; Influenza virus; Neuraminidases inhibitors; Synthesis