title: Human sialidase inhibitors: design, synthesis, and biological evaluation of 4-acetamido-5-acylamido-2-fluoro benzoic acids.
abstract: Recent advances in the sialidase biology have clarified the role of human sialidases (NEU 1 to NEU4) in the development of various disease states such as cancer, diabetes and arteriosclerosis. Isoform selective human sialidase inhibitors could be a therapeutic tool or molecular probes for the exploration of the specific functions of human sialidases. In the present study, de novo design based virtual screening was performed to find a new class of human sialidase inhibitors using the experimental crystal structure of NEU2 isoform. A few of nitro benzene and fluoro benzoic acid were identified and a series of 4-acetamido-5-acylamido-2-fluoro benzoic acids were synthesized and, the inhibitory activity of all these compounds against all human sialidase enzymes was evaluated. All these compounds were found to have a poor inhibitory activity and only NEU2 showed more sensitivity to this series of compounds as compared to other isoforms. Molecular docking was performed to gain insight regarding the binding mode of these inhibitors and thereby provided valuable information for our study on the design of selective human sialidase inhibitors further.
authors.affiliation: Department of Applied Bioorganic Chemistry, Faculty of Applied Biological Sciences, Gifu University, Japan. sadagopan_magesh@yahoo.com
authors.forename: Sadagopan
authors.initials: S
authors.lastname: Magesh
authors.forename: Vats
authors.initials: V
authors.lastname: Savita
authors.forename: Setsuko
authors.initials: S
authors.lastname: Moriya
authors.forename: Tohru
authors.initials: T
authors.lastname: Suzuki
authors.forename: Taeko
authors.initials: T
authors.lastname: Miyagi
authors.forename: Hideharu
authors.initials: H
authors.lastname: Ishida
authors.forename: Makoto
authors.initials: M
authors.lastname: Kiso
mesh_terms: D010129:4-Aminobenzoic Acid / Q000138:chemical synthesis / Q000494:pharmacology; D000083:Acetanilides / Q000138:chemical synthesis* / Q000494:pharmacology*; D002460:Cell Line; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D011485:Protein Binding; D013329:Structure-Activity Relationship; D062366:para-Aminobenzoates
chemical_list: D000083:Acetanilides; D062366:para-Aminobenzoates; C403285:NEU2 protein, human; D009439:Neuraminidase; D010129:4-Aminobenzoic Acid