Antiviral phenolics from the leaves of Cleistocalyx operculatus

TY - JOUR

T1 - Antiviral phenolics from the leaves of Cleistocalyx operculatus

AU - Ha, Thi Kim Quy

AU - Dao, Trong Tuan

AU - Nguyen, Ngoc Hieu

AU - Kim, Jiwon

AU - Kim, Eunhee

AU - Cho, Tae Oh

AU - Oh, Won Keun

N1 - Copyright © 2016 Elsevier B.V. All rights reserved.

PY - 2016/4

Y1 - 2016/4

N2 - 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.

AB - 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.

KW - Acetophenones

KW - Animals

KW - Antiviral Agents

KW - Dogs

KW - Enzyme Inhibitors

KW - Flavonoids

KW - HEK293 Cells

KW - Humans

KW - Influenza A Virus, H1N1 Subtype

KW - Influenza A Virus, H9N2 Subtype

KW - Inhibitory Concentration 50

KW - Madin Darby Canine Kidney Cells

KW - Molecular Structure

KW - Neuraminidase

KW - Plant Leaves

KW - Syzygium

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.fitote.2016.03.006

DO - 10.1016/j.fitote.2016.03.006

M3 - Journal article

C2 - 26972228

SN - 1971-551X

VL - 110

SP - 135

EP - 141

JO - Fitoterapia

JF - Fitoterapia

ER -