title: Antiviral phenolics from the leaves of Cleistocalyx operculatus.
abstract: During the screening program for anti-influenza agents from medicinal plants, the ethanolic extract of Cleistocalyx operculatus leaves was found to exhibit potential neuraminidase (NA) inhibitory activity. Bioassay-directed fractionation led to the isolation of two new acetophenones (1 and 2) and one new flavanone (3), along with six known compounds (4-9). The structures of all isolated compounds were elucidated using various spectroscopic methods and through comparison with the previous literature. Compounds 6 and 8 exhibited strong enzymatic inhibition on various neuraminidases from different influenza viruses, including H1N1, H9N2, novel H1N1, and oseltamivir-resistant novel H1N1 (H274Y mutation) expressed in HEK293 cells (IC50 values ranging from 5.07 ± 0.94 μM to 9.34 ± 2.52 μM, respectively). Kinetic experiments revealed the non-competitive inhibitory mode of both compounds 6 and 8. Furthermore, these flavonoids reduced the cytopathic effect of the H1N1 virus in MDCK cells. The present study suggests the potential of two flavonoids (6 and 8) as new lead compounds for the development of novel NA inhibitors in the future.
authors.affiliation: Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Thi Kim Quy
authors.initials: TK
authors.lastname: Ha
authors.affiliation: Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Trong Tuan
authors.initials: TT
authors.lastname: Dao
authors.affiliation: Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Ngoc Hieu
authors.initials: NH
authors.lastname: Nguyen
authors.affiliation: Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Jiwon
authors.initials: J
authors.lastname: Kim
authors.affiliation: Choong Ang Vaccine Laboratory, 59-3 Hwaam-dong, Yuseong-gu, Daejeon 305-348, Republic of Korea.
authors.forename: Eunhee
authors.initials: E
authors.lastname: Kim
authors.affiliation: Marine Bio Research Center, Department of Life Science, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Tae Oh
authors.initials: TO
authors.lastname: Cho
authors.affiliation: Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: wkoh1@snu.ac.kr.
authors.forename: Won Keun
authors.initials: WK
authors.lastname: Oh
mesh_terms: D000098:Acetophenones / Q000737:chemistry* / Q000302:isolation & purification; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000302:isolation & purification; D004285:Dogs; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000302:isolation & purification; D005419:Flavonoids / Q000737:chemistry* / Q000302:isolation & purification; D057809:HEK293 Cells; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects; D053127:Influenza A Virus, H9N2 Subtype / Q000187:drug effects; D020128:Inhibitory Concentration 50; D061985:Madin Darby Canine Kidney Cells; D015394:Molecular Structure; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D018515:Plant Leaves / Q000737:chemistry; D027842:Syzygium / Q000737:chemistry*
chemical_list: D000098:Acetophenones; D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D005419:Flavonoids; D009439:Neuraminidase
keywords: Cleistocalyx operculatus; H1N1; Influenza neuraminidase; Myrtaceae