A Study On Synthesis, Biological Activities and Molecular Modelling of Some Novel Trisubstituted 1,2,4‐Triazole Derivatives

Abstract

In this study, 1‐(4‐substitued benzyl)‐3,5‐diphenyl‐1H‐1,2,4‐triazoles (2 a‐e) and ethyl(3,5‐diphenyl‐1H‐1,2,4‐triazole‐1‐yl)acetate (3) were synthesized starting from 3,5‐diphenyl‐1H‐1,2,4‐triazole (1). The ethyl acetate derivative (3) was converted to 2‐(3,5‐diphenyl‐1H‐1,2,4‐triazole‐1‐yl)acetohydrazide (4) in ethanolic medium with hydrazine hydrate. The reaction of the acetohydrazide (4) with suitable isothiocyanates generate 2‐[(3, 5‐diphenyl‐1H‐1,2,4‐triazole‐1‐yl)acetyl]‐4‐methyl/phenyhlthiosemicarbazide (5 a,b). The cyclization of the thiosemicarbazide (5 a,b) in the presence of NaOH (2 M) resulted in the formation of 5‐[(3, 5‐diphenyl‐1H‐1,2,4‐triazole‐1‐yl)methyl]‐4‐methyl/phenyl‐2,4‐dihidro‐3H‐1,2,4‐triazole‐3‐thiol (6 a,b). Finally, the synthesized 1,2,4‐triazole‐3‐thiols (6 a,b) were converted to their S‐substituebenzyl derivatives (7 a‐j). All of the synthesized compounds (1‐7) were also examined for antioxidant capacities, and antiurease and anti‐acetylcholinesterase (anti‐AChE) activities. It has been found that antioxidant capacity and anti‐urease activity of the compound 7 f is very good in biochemically active compounds.

SEM morphological analysis of irradiated polystyrene film doped by a Schiff base containing a 1,2,4-triazole ring system

“…The Schiff base chosen is novel, easy to synthesize, highly aromatic and incorporates phenyl, benzyl, a meta-substituted aryl ring, and 1,2,4-triazole, which provide all the necessary elements for a good photostabilizer. Heterocycles containing the 1,2,4-triazole moiety have various biological activities [18][19][20][21]. The Schiff base enhances the photostability of PS against photodegradation that is a continuation of previously reported work in the area of polymers [22][23][24][25][26][27][28][29][30][31][32][33].…”

Recent Advances in 1,2,4‐Triazole Scaffolds as Antiviral Agents

“…[58] Notably, the nucleoside compounds with a rigid triple bond, whether they have cyclic sugar or not, exhibited highly potent antiviral activity comparable or even more effective than the reference drugs. For example, compounds bearing arylethynyltriazolyl as nucleobase entities (34)(35)(36) act as hit and potent lead antiviral candidates that have been subjected to several structural modifications ( Figure 10). [59] Chudinov and co-workers focused on the structure-activity relationship of 5-arylvinyl analogs with substituents at the 5th position of the triazole ring and the antiviral activity.…”

“…[34] Moreover, 1,2,4-triazole nucleus displays stability towards each chemical as well as metabolic degradation and can be able to enhance the solubility of the ligand, besides it can substantially improve pharmacokinetics (absorption, distribution, metabolism, and excretion) along with pharmacodynamic properties of the drug because of its polar nature. [35,36] Ribavirin (16) and its analogs, Levovirin (17), and Viramidine (18) are antiviral drugs containing 1,2,4-triazole scaffolds (Figure 4). Ribavirin (Virazole, 1-β-D-ribofuranosyl-1,2,4-triazole-3carboxamide) is a unique antiviral nucleoside agent with a broad antiviral spectrum used against both RNA and DNA viruses, involving influenza A and B types [37] as well as poxviruses.…”

“…Accordingly, 1,2,4‐ triazoles are employed as amide bond bioisosteres due to the similarity in hydrogen bond accepting capability, dipole moment, size, and with an additional benefit of good metabolic stability lacking in the amide bond . Moreover, 1,2,4‐triazole nucleus displays stability towards each chemical as well as metabolic degradation and can be able to enhance the solubility of the ligand, besides it can substantially improve pharmacokinetics (absorption, distribution, metabolism, and excretion) along with pharmacodynamic properties of the drug because of its polar nature …”

Synthesis, Study of the Biological Activity of New 1,2,4‐Triazole Derivatives and Characteristics of the Relationship of the Structure and Biological Activity in a Series of the Latter

“…Analysis of the literature data shows that the intensity of research in this area is likely to increase, revealing new useful properties, expanding the existing wide range of biological effects of 1,2,4‐triazole derivatives. Recent studies have found that new representatives of this series revealed antimicrobial,– antibacterial,– anti‐fungal,– anticonvulsant,– antitumor,– antioxidant, activities, specific activity against influenza A/H1 N1, growth‐stimulating, herbicidal, insecticidal, anti‐tuberculosis, anticholinesterase activities. They inhibit the interaction of annexin A2 and protein S100 A10, HIV 1 replication, p38 MAР kinase, HDAC‐tabulin,– adenosine receptor antagonists, agents in the treatment of Alzheimer's disease, ion channel modulators, etc.…”