title: Novel biphenyl ester derivatives as tyrosinase inhibitors: Synthesis, crystallographic, spectral analysis and molecular docking studies.
abstract: Biphenyl-based compounds are clinically important for the treatments of hypertension and inflammatory, while many more are under development for pharmaceutical uses. In the present study, a series of 2-([1,1'-biphenyl]-4-yl)-2-oxoethyl benzoates, 2(a-q), and 2-([1,1'-biphenyl]-4-yl)-2-oxoethyl pyridinecarboxylate, 2(r-s) were synthesized by reacting 1-([1,1'-biphenyl]-4-yl)-2-bromoethan-1-one with various carboxylic acids using potassium carbonate in dimethylformamide at ambient temperature. Single-crystal X-ray diffraction studies revealed a more closely packed crystal structure can be produced by introduction of biphenyl moiety. Five of the compounds among the reported series exhibited significant anti-tyrosinase activities, in which 2p, 2r and 2s displayed good inhibitions which are comparable to standard inhibitor kojic acid at concentrations of 100 and 250 μg/mL. The inhibitory effects of these active compounds were further confirmed by computational molecular docking studies and the results revealed the primary binding site is active-site entrance instead of inner copper binding site which acted as the secondary binding site.
authors.affiliation: School of Chemical Sciences, Universiti Sains Malaysia, Penang, Malaysia.
authors.forename: Huey Chong
authors.initials: HC
authors.lastname: Kwong
authors.affiliation: Department of Engineering Chemistry, Vidya Vikas Institute of Engineering & Technology, Visvesvaraya Technological University, Alanahalli, Mysuru, Karnataka, India.
authors.forename: C S
authors.initials: CS
authors.lastname: Chidan Kumar
authors.affiliation: School of Biosciences, Taylor's University, Lakeside Campus, Subang Jaya, Selangor, Malaysia.
authors.forename: Siau Hui
authors.initials: SH
authors.lastname: Mah
authors.affiliation: X-ray Crystallography Unit, School of Physics, Universiti Sains Malaysia, Penang, Malaysia.
authors.forename: Tze Shyang
authors.initials: TS
authors.lastname: Chia
authors.affiliation: X-ray Crystallography Unit, School of Physics, Universiti Sains Malaysia, Penang, Malaysia.
authors.forename: Ching Kheng
authors.identifier: http://orcid.org/0000-0002-3279-4349
authors.initials: CK
authors.lastname: Quah
authors.affiliation: School of Biosciences, Taylor's University, Lakeside Campus, Subang Jaya, Selangor, Malaysia.
authors.forename: Zi Han
authors.initials: ZH
authors.lastname: Loh
authors.affiliation: Department of Sugar Technology & Chemistry, Sir M.V. PG Center, University of Mysore, Tubinakere, India.
authors.forename: Siddegowda
authors.initials: S
authors.lastname: Chandraju
authors.affiliation: School of Chemical Sciences, Universiti Sains Malaysia, Penang, Malaysia.
authors.forename: Gin Keat
authors.initials: GK
authors.lastname: Lim
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D001713:Biphenyl Compounds / Q000138:chemical synthesis*; D020134:Catalytic Domain; D003300:Copper / Q000737:chemistry; D018360:Crystallography, X-Ray; D004952:Esters / Q000138:chemical synthesis*; D016018:Least-Squares Analysis; D062105:Molecular Docking Simulation; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011753:Pyrones / Q000737:chemistry; D012984:Software; D012997:Solvents; D013055:Spectrophotometry, Infrared; D013696:Temperature; D014961:X-Ray Diffraction
chemical_list: D001713:Biphenyl Compounds; D003300:Copper; D004952:Esters; D014442:Monophenol Monooxygenase; D011753:Pyrones; D012997:Solvents; C010574:biphenyl; C011890:kojic acid