Butylated hydroxytoluene analogs: synthesis and evaluation of their multipotent antioxidant activities.
A computer-aided predictions of antioxidant activities were performed with the Prediction Activity Spectra of Substances (PASS) program. Antioxidant activity of compounds 1, 3, 4 and 5 were studied using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and lipid peroxidation assays to verify the predictions obtained by the PASS program. Compounds 3 and 5 showed more inhibition of DPPH stable free radical at 10⁻⁴ M than the well-known standard antioxidant, butylated hydroxytoluene (BHT). Compound 5 exhibited promising in vitro inhibition of Fe²⁺-induced lipid peroxidation of the essential egg yolk as a lipid-rich medium (83.99%, IC₅₀ 16.07 ± 3.51 μM/mL) compared to α-tocopherol (α-TOH, 84.6%, IC₅₀ 5.6 ± 1.09 μM/mL). The parameters for drug-likeness of these BHT analogues were also evaluated according to the Lipinski’s “rule-of-five” (RO5). All the BHT analogues were found to violate one of the Lipinski’s parameters (LogP > 5), even though they have been found to be soluble in protic solvents. The predictive polar surface area (PSA) and absorption percent (% ABS) data allow us to conclude that they could have a good capacity for penetrating cell membranes. Therefore, one can propose these new multipotent antioxidants (MPAOs) as potential antioxidants for tackling oxidative stress and lipid peroxidation processes.
Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia.
Wageeh A
WA
Yehye
Noorsaadah
N
Abdul Rahman
Abeer A
AA
Alhadi
Hamid
H
Khaledi
Ng Seik
NS
Weng
Azhar
A
Ariffin
D000975:Antioxidants / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000737:chemistry; D002084:Butylated Hydroxytoluene / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006860:Hydrogen Bonding / Q000187:drug effects; D020128:Inhibitory Concentration 50; D015227:Lipid Peroxidation / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D010851:Picrates / Q000737:chemistry; D013237:Stereoisomerism
D000975:Antioxidants; D001713:Biphenyl Compounds; D016861:Cyclooxygenase Inhibitors; D016166:Free Radical Scavengers; D010851:Picrates; D002084:Butylated Hydroxytoluene; C004931:1,1-diphenyl-2-picrylhydrazyl