title: Potential New H1N1 Neuraminidase Inhibitors from Ferulic Acid and Vanillin: Molecular Modelling, Synthesis and in Vitro Assay.
abstract: 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 IC50of 50 μM. In contrast, the virus inhibition assay showed MY15, a ferulic acid derivative has the best activity with the EC50of ~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 ΔGbindvalues comparable to those of oseltamivir and zanamivir, the two commercial NA inhibitors.
authors.affiliation: School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Minden, Pulau Pinang, Malaysia.
authors.forename: Maywan
authors.initials: M
authors.lastname: Hariono
authors.affiliation: School of Health Sciences, Universiti Sains Malaysia, 16150 Kubang Krian, Kelantan, Malaysia.
authors.forename: Nurshariza
authors.initials: N
authors.lastname: Abdullah
authors.affiliation: School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Minden, Pulau Pinang, Malaysia.
authors.forename: K V
authors.initials: KV
authors.lastname: Damodaran
authors.affiliation: School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Minden, Pulau Pinang, Malaysia.
authors.forename: Ezatul E
authors.initials: EE
authors.lastname: Kamarulzaman
authors.affiliation: School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Minden, Pulau Pinang, Malaysia.
authors.forename: Nornisah
authors.initials: N
authors.lastname: Mohamed
authors.affiliation: Jeffry Cheah School of Medicine and Health Sciences, Monash University Malaysia, 47500 Bandar Sunway, Selangor Darul Islam, Malaysia.
authors.forename: Sharifah Syed
authors.initials: SS
authors.lastname: Hassan
authors.affiliation: School of Health Sciences, Universiti Sains Malaysia, 16150 Kubang Krian, Kelantan, Malaysia.
authors.forename: Shaharum
authors.initials: S
authors.lastname: Shamsuddin
authors.affiliation: School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Minden, Pulau Pinang, Malaysia.|Malaysian Institute of Pharmaceuticals and Nutraceuticals, Ministry of Science, Technology and Innovation, Halaman Bukit Gambir, 11900 Bayan Lepas, Pulau Pinang, Malaysia.
authors.forename: Habibah A
authors.initials: HA
authors.lastname: Wahab
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001547:Benzaldehydes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D001681:Biological Assay; D003373:Coumaric Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000201:enzymology*; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D001547:Benzaldehydes; D003373:Coumaric Acids; D004791:Enzyme Inhibitors; C004999:ferulic acid; C100058:vanillin; D009439:Neuraminidase