Butylated Hydroxytoluene Analogs: Synthesis and Evaluation of Their Multipotent Antioxidant Activities

Molecules

Wageeh A. Yehye¹  Noorsaadah Abdul Rahman¹  Abeer A. Alhadi¹  Hamid Khaledi¹  Seik Weng Ng¹ 

[1] ¹Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia ²Chemistry Department, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia

关键词: butylated hydroxyltolouene;    drug-likeness properties;    DPPH;    lipid peroxidation;    multipotent antioxidant;    rule-of-five;    PASS and activity prediction;    thiosemicarbazide;    1;    2;    4-triazole;    1;    3;    4-thiadiazole;   

DOI  :  10.3390/molecules17077645

来源: mdpi

【 摘 要 】

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 a-tocopherol (a-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.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.