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. 2016 Jun 28;21(7):847.
doi: 10.3390/molecules21070847.

Rational Design and Synthesis of New, High Efficiency, Multipotent Schiff Base-1,2,4-triazole Antioxidants Bearing Butylated Hydroxytoluene Moieties

Wageeh A Yehye  1 , Noorsaadah Abdul Rahman  2   3 , Omar Saad  4 , Azhar Ariffin  5 , Sharifah Bee Abd Hamid  6 , Abeer A Alhadi  7   8 , Farkaad A Kadir  9 , Marzieh Yaeghoobi  10   11 , Abdulsalam A Matlob  12
Affiliations

Rational Design and Synthesis of New, High Efficiency, Multipotent Schiff Base-1,2,4-triazole Antioxidants Bearing Butylated Hydroxytoluene Moieties

Wageeh A Yehye et al. Molecules. .

Abstract

A new series of multipotent antioxidants (MPAOs), namely Schiff base-1,2,4-triazoles attached to the oxygen-derived free radical scavenging moiety butylated hydroxytoluene (BHT) were designed and subsequently synthesized. The structure-activity relationship (SAR) of the designed antioxidants was established alongside the prediction of activity spectra for substances (PASS). The antioxidant activities of the synthesized compounds 4-10 were tested by the DPPH bioassay. The synthesized compounds 4-10 inhibited stable DPPH free radicals at a level that is 10(-4) M more than the well-known standard antioxidant BHT. Compounds 8-10 with para-substituents were less active than compounds 4 and 5 with trimethoxy substituents compared to those with a second BHT moiety (compounds 6 and 7). With an IC50 of 46.13 ± 0.31 µM, compound 6 exhibited the most promising in vitro inhibition at 89%. Therefore, novel MPAOs containing active triazole rings, thioethers, Schiff bases, and BHT moieties are suggested as potential antioxidants for inhibiting oxidative stress processes and scavenging free radicals, hence, this combination of functions is anticipated to play a vital role in repairing cellular damage, preventing various human diseases and in medical therapeutic applications.

Keywords: 1,2,4-triazole; DPPH assay; PASS; Schiff base; butylated hydroxytoluene.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Rational design of Schiff base-1,2,4-triazoles bearing BHT moieties.
Scheme 1
Scheme 1
Synthetic scheme for the formation of 4-amino-3-((3,5-di-tert-butyl-4-hydroxybenzylthio)methyl)-1H-1,2,4-triazole-5(4H)-thione (3).
Scheme 2
Scheme 2
Synthetic scheme for the formation of 4-(substituted benzylideneamino)-3-((3,5-di-tert-butyl-4-hydroxybenzyl thio)methyl)-1H-1,2,4-triazole-5(4H)-thiones 4–10.
Figure 2
Figure 2
Proposed intra-molecular hydrogen bonding of 7.
Scheme 3
Scheme 3
Proposed mechanism for BHT/DPPH• reaction.
Figure 3
Figure 3
Transition state of hydrogen abstraction by ROS.
Figure 4
Figure 4
Steric hindrance effects on stabilization of phenoxyl radical [57].
Figure 5
Figure 5
Thione I and thiol II tautomers of 4-amino-1,2,4-triazol-5-thione.
See this image and copyright information in PMC

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