New s-Triazine/Tetrazole conjugates as potent antifungal and antibacterial agents: Design, molecular docking and mechanistic study

A novel hybrid N-2-(tetrazol-5-yl)-6-substituted-5,6-dihydro-1,3,5-triazine-2,4-diamines have been synthesized in excellent yields through one-pot multi-component reaction of 5-amino-1,2,3,4-tetrazole, cyanamide and aromatic/heteroaromatic aldehydes in acetic acid promoted by controlled microwave heating. All the obtained heterocycles were screened for their antimicrobial and antifungal activities. New series ( 4a-j ) were developed through binding of s-triazine and tetrazole in one compact structure. The tested compounds showed excellent antibacterial activity against the Gram-negative bacterial strains, P. aeruginosa and E. coli compared to ciprofloxacin. The same derivatives experienced high outstanding activity against C. albicans compared to Fluconazole. Investigation of the mode of action as antibacterial agents revealed that the most active compound 4a has good inhibitory effect for DNA gyrase and topoisomerase IV ATPase and E. coli TOPO IV and DNA gyrase supercoiling. Additionally, 4a and 4g showed good in vitro inhibitory activity to lanosterol 14-alpha-demethylase (CYP51 protein) and good fitting to the same protein as possible antifungal target. Similarly, the target compounds have acceptable ADME and drug-likeness properties without any violation. Hence, new highly potent antibacterial and antifungal candidates were introduced that require further optimization. (c) 2022 Elsevier B.V. All rights reserved.

Automated summary

A novel class of heterocyclic compounds was synthesized using a convenient synthetic method, and their antimicrobial and antifungal activities were screened. The results showed that these compounds exhibited strong antibacterial and antifungal properties against certain bacteria and fungi, and demonstrated good drug-likeness.