title: Synthesis and anti-influenza activities of novel baicalein analogs.
abstract: A series of novel flavones derivatives were synthesized based on modification of the active ingredients of a traditional Chinese medicine Scutellaria baicalensis GEORGI and screened for anti-influenza activity. The synthetic baicalein (flavone) analogs, especially with the B-rings substituted with bromine atoms, were much more potent than oseltamivir or ribavirin against H1N1 Tamiflu-resistant (H1N1 TR) virus and usually with more favorable selectivity. The most promising were 5b, 5c, 6b and 6c, all displaying an 50% effective concentration (EC50) at around 4.0-4.5 µM, and a selective index (SI=50% cytotoxic concentration (CC50)/EC50)>70. For seasonal H3N2-infected influenza virus, both 5a and 5b with SI >17.3 indicated superior to ribavirin. The flavonoids having both not-naturally-occurring bromo-substituted B-rings and appropriate hydroxyls positioning on the A-rings might be critical in determining the activity and selectivity against H1N1-Tamiflu-resistant infected influenza viruses.
authors.affiliation: Institute of Medical Sciences, National Defense Medical Center.
authors.forename: Shu-Ting
authors.initials: ST
authors.lastname: Chung
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Chien
authors.forename: Wen-Hsin
authors.initials: WH
authors.lastname: Huang
authors.forename: Chen-Wen
authors.initials: CW
authors.lastname: Yao
authors.forename: An-Rong
authors.initials: AR
authors.lastname: Lee
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D044950:Flavanones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D031364:Scutellaria baicalensis / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D044950:Flavanones; C006680:baicalein