Synthesis and Characterization of Double-headed Heterocycles of 1,2,4- triazole: Antitumor and Antimicrobial Evaluation

Introduction: Ribavirin is a 1,2,4-triazole nucleoside that has been used to treat hepatitis C virus infections. Previous studies have revealed a number of biological actions of 1,2,4-triazole and its Schiff bases, including herbicidal, fungicidal, anticancer, and antiviral activity. With readily available laboratory reagents, tartaric acid, and mercaptotriazolethanediol derivative, the authors aimed to synthesize and characterize some novel Schiff bases of the 1,2,4-triazole skeleton. Schiff bases are adaptable substances with a wide range of uses in biology and chemistry. Methods: For obtaining Schiff bases of 1,2,4-triazole derivatives, the strategy involved synthesizing bis-mercapto-1,2,4- or/and 4-amino-5-(benzylthio)1,2,4-triazole and then reacting it with aromatic aldehydes, such as furfural, 4-amino N, N-dimethylbenzaldehyde, 4-cyanobenzaldehyde, 2,4- dichlorobenzaldehyde, and 4-hydroxybenzaldehyde in MeOH/HCl. The prepared structures were confirmed using IR, 1H/13C NMR, and elemental analysis. The antimicrobial activity of the synthesized compounds was investigated against Gram +ve and Gram -ve bacteria, fungi, and yeast. Moreover, antitumor activity was tested for some compounds against one tumor cell line (MCF-7 cell line). Results: Schiff bases of some double-headed acyclic nucleosides of 1,2,4-triazole were synthesized with high yields in the range 52%-87%. Compounds 6, 7, 11, and 16 exhibited high antimicrobial activity. Compound 12 was considered the most active one, and it can potentially act as an antimicrobial agent compared with the standard references, Gentamycin and fluconazole. Finally, compounds 8 and 12 exhibited high antitumor activity. Compound 8 showed antitumor activity more than the reference drug cisplatin. Discussion: The structure of the synthesized Schiff bases of double-headed acyclic nucleosides of 1,2,4-triazole was established using elemental analysis, IR, MS, and 1H/13C NMR spectroscopy. The activity of Schiff bases was significantly influenced by the substituent groups of the aromatic ring, particularly electron-donating and electron-withdrawing groups. Conclusion: The authors recommend further experimental assessments of compounds 8 and 12 as antimicrobial and antitumor agents, considering their promising biological results.