TY - JOUR
T1 - Potential new H1N1 neuraminidase inhibitors from ferulic acid and vanillin
T2 - Molecular modelling, synthesis and in vitro assay
AU - Hariono, Maywan
AU - Abdullah, Nurshariza
AU - Damodaran, K. V.
AU - Kamarulzaman, Ezatul E.
AU - Mohamed, Nornisah
AU - Hassan, Sharifah Syed
AU - Shamsuddin, Shaharum
AU - Wahab, Habibah A.
N1 - Funding Information:
We gratefully acknowledge the Malaysian Ministry of Science and Technology Innovation (02-05-23-SF0012) for the financial support of this work. MH gratefully acknowledged Universiti Sains Malaysia and grant No 02-05-23-SF0019 for the Graduate Research Assistantship (2013-2015).
Publisher Copyright:
© The Author(s) 2016.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2016/12/20
Y1 - 2016/12/20
N2 - We report the computational and experimental efforts in the design and synthesis of novel neuraminidase (NA) inhibitors from ferulic acid and vanillin. Two proposed ferulic acid analogues, MY7 and MY8 were predicted to inhibit H1N1 NA using molecular docking. From these two analogues, we designed, synthesised and evaluated the biological activities of a series of ferulic acid and vanillin derivatives. The enzymatic H1N1 NA inhibition assay showed MY21 (a vanillin derivative) has the lowest IC50 of 50 μM. In contrast, the virus inhibition assay showed MY15, a ferulic acid derivative has the best activity with the EC50 of ∼0.95 μM. Modelling studies further suggest that these predicted activities might be due to the interactions with conserved and essential residues of NA with ΔGbind values comparable to those of oseltamivir and zanamivir, the two commercial NA inhibitors.
AB - We report the computational and experimental efforts in the design and synthesis of novel neuraminidase (NA) inhibitors from ferulic acid and vanillin. Two proposed ferulic acid analogues, MY7 and MY8 were predicted to inhibit H1N1 NA using molecular docking. From these two analogues, we designed, synthesised and evaluated the biological activities of a series of ferulic acid and vanillin derivatives. The enzymatic H1N1 NA inhibition assay showed MY21 (a vanillin derivative) has the lowest IC50 of 50 μM. In contrast, the virus inhibition assay showed MY15, a ferulic acid derivative has the best activity with the EC50 of ∼0.95 μM. Modelling studies further suggest that these predicted activities might be due to the interactions with conserved and essential residues of NA with ΔGbind values comparable to those of oseltamivir and zanamivir, the two commercial NA inhibitors.
UR - http://www.scopus.com/inward/record.url?scp=85006829781&partnerID=8YFLogxK
U2 - 10.1038/srep38692
DO - 10.1038/srep38692
M3 - Article
C2 - 27995961
AN - SCOPUS:85006829781
SN - 2045-2322
VL - 6
JO - Scientific Reports
JF - Scientific Reports
M1 - 38692
ER -