SYNTHESIS, ANTIMICROBIAL EVALUATION, MOLECULARDOCKING, AND TOXICITY PREDICTIONOFN-BENZYLIDENE-1,2,4-TRIAZOLO[4,3-b]PYRIDAZINEDERIVATIVES

Abstract

A total of eleven novel N-benzylidene-[1,2,4]triazolo[4,3-b]pyridazine derivatives (5a–5k) were synthesisedandstructurally characterised by 1H NMR, ¹³C NMR, and mass spectroscopy. All eleven scaffolds were screened against a panel of bacterial and fungal pathogens to assess their antimicrobial activity. Several newly synthesised derivativespossessed substantial inhibitory effects which are comparable to those of the reference drugs. Because of theextensive pharmacological potential of 1,2,4-triazole derivatives, computational docking studies were performedonall the synthesised scaffolds to investigate their binding interactions with the β-catenin protein (PDB ID: 1JDH), atherapeutically relevant molecular target involved in cancer progression. Compounds 5e, 5f, 5g, and 5h exhibitedfavourable binding scores similar to the reference inhibitor FH-535. To further explore, toxicity prediction usingProTox-3.0 was carried out to assess the safety profile of the selected compounds, suggesting acceptable safetylimits. However, the continuous emergence of antimicrobial resistance highlights the urgent need for structurallydiverse and effective antimicrobial agents. The comprehensive results based on the experimental and computational approaches revealed that these novel hybrids (5a-5k) represent promising scaffolds for the development of antimicrobial and other useful therapeutic drugs, thereby contributing to United Nations Sustainable Development Goal 3: Good Health and Well-being.