Sulfide-linked 3,4,5-trimethoxyphenyl-thiosemicarbazide/triazole hybrids: Synthesis, antioxidant, antiglycation, DNA cleavage and DNA molecular docking studies

The synthesis of disubstituted 4-methyl-N,N-dipropylbenzenamine derivatives bearing identical azolethione(thiol) moieties as antioxidant agents

“…The activity comparison in the pair of thiosemicarbazide 3triazolethione 5 follows the same pattern as in the case of 4 and 6, respectively. This structure-activity relationship corresponds to the reported signi cant decrease of activity of triazole in comparison with the one of thiosemicarbazide [11]. One of the reasonable explanations for the higher antioxidant activity of thiosemicarbazides is the existence of the thiourea fragment, which stabilizes free radicals of nitrogen atoms by double conjugation, mainly with the C = S group.…”

“…In the 13 C NMR spectrum for 8, carbon C 11,11' resonated at 35.9 ppm. Hydrazone derivatives 3,3'-((p-tolylazanediyl)bis(ethane-2,1-diyl))bis(4-((4-(dimethylamino)benzylidene)amino)-1H-1,2,4-triazole-5(4H)-thione) (10) and 3,3'-((ptolylazanediyl)bis(ethane-2,1-diyl))bis(4-(4-methoxybenzylideneamino)-1H-1,2,4-triazole-5(4H)-thione) (11) were synthesised from 5,5'-((p-tolylazanediyl)bis(ethane-2,1-diyl))bis(4-amino-2,4-dihydro-3H-1,2,4triazole-3-thione) (9) [42] and 4-(dimethylamino)benzaldehyde or 4-methoxybenzaldehyde, respectively, in methanol in the presence of hydrochloric acid in excellent yield (Scheme 2). In the 1 H NMR spectra for 10 and 11, singlets at 9.33 ppm and 9.63 ppm, respectively, have been attributed each to two H 11 protons in 4-substituted benzylideneamine moieties, proving the formation of the target structures.…”

“…It can be assumed, that the lower stability of such a radical is responsible for a weaker antioxidant activity. Another reasonable explanation may be based on the decreased number of NH bonds upon the formation of the 1,2,4-thriazole ring and more limited electron delocalisation across the aromatic ring [11].…”

“…Among them, the nitrogen-containing ve-membered triazole moiety has been distinguished as a remarkable heterocyclic moiety, possessing various pharmacological properties, which could play a major role in the common mechanisms associated with various disorders such as cancer, in ammation, convulsions, neurodegeneration, and oxidative stress [9]. 1,2,4-Triazole derivatives have been shown to possess a series of important pharmacological properties such as antioxidant [10][11][12][13][14][15][16], antibacterial [15,[17][18][19][20], antifungal [21,22], antiviral [23], anticancer [15,[24][25][26][27],…”

“…Combining two or more bioactive moieties into a single molecule is a commonly used strategy in drug design to improve pharmacological properties [11]. The potency of the antioxidant agent can be enhanced by combining two or even more structural and functional fragments with proven antioxidant activity.…”