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

Abstract

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.

Unexpected cleavage of C–S bond in the hydrazination of 2-((3,5-di- tert -butyl-4-hydroxybenzyl)thio) nicotinate: synthesis and mechanistic studies by kinetic and computational approaches

“…15 No C-S bond cleavage was observed in that reaction. 15 However hydrazination of ester 4 does not proceed as expected, instead compounds 5a and 5b were isolated.…”

“…15 No C-S bond cleavage was observed in that reaction. 15 However hydrazination of ester 4 does not proceed as expected, instead compounds 5a and 5b were isolated. The observed products, 5a and 5b in Scheme 2 could be attributed to the stability of the resulting intermediate, quinone methide.…”

“…13,15,17 However when we reacted ester 4 (Scheme 1) in alcoholic solutions, the expected hydrazide 5 was not isolated. Instead an unexpected cleavage of the C-S bond occurred, leading to the formation of compounds 5a and 5b as shown in Scheme 2.…”

“…Liu et al 14 has utilized the hydrazination process as one of the steps in the preparation of triazolinethione, 8, an example of 5-membered heterocyclic compound. Wageeh et al 15 also utilized the hydrazination of an ester as one of the steps in the preparation of 1,2,4-triazole, 9.…”

Synthesis and molecular docking studies of a new series of bipyrazol-yl-thiazol-ylidene-hydrazinecarbothioamide derivatives as potential antitubercular agents

“…The incessant stage of mycobacterial infection stands as one of the biggest challenge in management of tuberculosis treatment; this is the phase in bacterial lifecycle when it is considered to be in a slowgrowing or non-growing state 6 . Hydrazinecarbothioamides or thiosemicarbazones consist of an imperative class of nitrogen and sulfur containing compounds, and have acknowledged huge attention owing to their notable biological and pharmacological properties, such as antimycobacterial 9 , antioxidant 10,11 , antibacterial 12 , antiviral, antiamoebic, and antitumor 13 , analgesic, anti-inflammatory 14 and antifungal 15 . Considering this fact, multidrug therapies of longer durations are prescribed in tuberculosis medication.…”