title: Correlation of antioxidant activities with theoretical studies for new hydrazone compounds bearing a 3,4,5-trimethoxy benzyl moiety.
abstract: A new series of antioxidants, namely imines bearing the well-known free radical scavenger group 3,4,5-trimethoxybenzyloxy, was designed and synthesized. Theoretical calculations based on density functional theory (DFT) were performed to understand the antioxidant activities. Experimental studies evaluating the antioxidant activities of the compounds using DPPH and FRAP assays verified the predictions obtained by DMOL3 based on DFT.1. The DPPH radical scavenging activities depended on the substitution pattern of the aromatic aldehyde, with both the substitution type and position showing significant effects. Compounds 7b, 7c and 7d, which contain a phenolic hydroxyl group at the para position to the imine as well as, additional electron donating groups at the ortho-position to this hydroxyl group, exhibited IC₅₀ values of 62, 75 and 106 μg/mL, respectively, and potent antioxidant activities against DPPH, which were better than that of the reference compound BHT. With the exception of compounds 7a and 7h with a phenolic hydroxyl group at the ortho position, all of the investigated compounds exhibited ferric reducing activities above 1000 μM. Correlation analysis between the two antioxidant assays revealed moderate positive correlation (r = 0.59), indicating differing antioxidant activities based on the reaction mechanism. Therefore, imines bearing a 3,4,5-trimethoxybenzyloxy group can be proposed as potential antioxidants for tackling oxidative stress.
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia; General Directorate of Curricula, Ministry of Education, Baghdad 3310, Iraq.
authors.forename: Huda S
authors.initials: HS
authors.lastname: Kareem
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia. Electronic address: azhar70@um.edu.my.
authors.forename: Azhar
authors.initials: A
authors.lastname: Ariffin
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia.
authors.forename: Nurdiana
authors.initials: N
authors.lastname: Nordin
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Heidelberg
authors.affiliation: Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia.
authors.forename: Azlina
authors.initials: A
authors.lastname: Abdul-Aziz
authors.affiliation: Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia.
authors.forename: Kin Weng
authors.initials: KW
authors.lastname: Kong
authors.affiliation: Nanotechnology & Catalysis Research Centre (NANOCAT), University of Malaya, Block 3A, Institute of Postgraduate Studies Building, Kuala Lumpur 50603, Malaysia.
authors.forename: Wageeh A
authors.initials: WA
authors.lastname: Yehye
mesh_terms: D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006835:Hydrazones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D018384:Oxidative Stress / Q000187:drug effects; D011789:Quantum Theory; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D006835:Hydrazones
keywords: Antioxidant; Bond dissociation energy (BDE); Hydrazone; Hydrogen atom transfer; Single electron transfer; Spin density (SD)