title: Synthesis and antioxidant activity of polyhydroxylated trans-restricted 2-arylcinnamic acids.
abstract: A series of sixteen polyhydroxylated trans-restricted 2-arylcinnamic acid analogues 3a-p were synthesized through a one-pot reaction between homophthalic anhydrides and various aromatic aldehydes, followed by treatment with BBr3. The structure of the newly synthesized compounds was confirmed by spectroscopic methods and the configuration around the double bond was unequivocally estimated by means of gated decoupling 13C-NMR spectra. It was shown that the trans-cinnamic acid fragment incorporated into the target compounds' structure ensures the cis-configuration of the stilbene backbone and prevents further isomerization along the carbon-carbon double bond. The antioxidant activity of compounds 3a-p was measured against 1,1-diphenyl-2-picrylhydrazyl (DPPH●), hydroxyl (OH●) and superoxide (O2●▬) radicals. The results obtained showed that the tested compounds possess higher activities than natural antioxidants such as protocatechuic acid, caffeic acid and gallic acid. Moreover, it was shown that a combination of two different and independently acting fragments of well-known pharmacological profiles into one covalently bonded hybrid molecule evoke a synergistic effect resulting in higher than expected activity. To rationalize the apparent antioxidant activity and to establish the mechanism of action, a SAR analysis and DFT quantum chemical computations were also performed.
authors: Faculty of Chemistry and Pharmacy, University of Sofia "St. Kliment. Ohridski", 1, James Bourchier Blvd., Sofia 1164, Bulgaria. lishpera_87@abv.bg.
authors: Mitko
authors: M
authors: Miliovsky
authors: Faculty of Chemistry and Pharmacy, University of Sofia "St. Kliment. Ohridski", 1, James Bourchier Blvd., Sofia 1164, Bulgaria. ivansvinyarov@abv.bg.
authors: Ivan
authors: I
authors: Svinyarov
authors: Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Science, Acad. G. Bonchev Str. Bl. 9, Sofia 1113, Bulgaria. elenatodorova90@gmail.com.
authors: Elena
authors: E
authors: Prokopova
authors: Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Science, Acad. G. Bonchev Str. Bl. 9, Sofia 1113, Bulgaria. danibat@orgchm.bas.bg.
authors: Daniela
authors: D
authors: Batovska
authors: Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Science, Acad. G. Bonchev Str. Bl. 9, Sofia 1113, Bulgaria. s_stoyanov@orgchm.bas.bg.
authors: Simeon
authors: S
authors: Stoyanov
authors: Faculty of Chemistry and Pharmacy, University of Sofia "St. Kliment. Ohridski", 1, James Bourchier Blvd., Sofia 1164, Bulgaria. mbogdanov@chem.uni-sofia.bg.
authors: Milen G
authors: MG
authors: Bogdanov
mesh_terms: D001713:Biphenyl Compounds / Q000737:chemistry; D002934:Cinnamates / Q000138:chemical synthesis*; D016166:Free Radical Scavengers / Q000138:chemical synthesis*; D062385:Hydroxybenzoates / Q000737:chemistry; D008956:Models, Chemical; D010851:Picrates / Q000737:chemistry; D011789:Quantum Theory; D017382:Reactive Oxygen Species / Q000737:chemistry
chemical_list: D001713:Biphenyl Compounds; D002934:Cinnamates; D016166:Free Radical Scavengers; D062385:Hydroxybenzoates; D010851:Picrates; D017382:Reactive Oxygen Species; C004931:1,1-diphenyl-2-picrylhydrazyl
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