Exploring the antimicrobial and pharmacokinetic properties, molecule docking of newly synthesized indole-thiadiazole derivatives

Abstract The present study employed a three-step synthetic strategy to develop a series of novel (Z)-N-(2,4-dimethylphenyl)-3-(3-(((5-phenyl-1,3,4-thiadiazol-2-yl) imino) methyl)-1H-indol-1-yl) propanamide derivatives. This approach utilized readily available and cost-effective reagents under mild reaction conditions, affording the target indole-based compounds in good yields. Structural elucidation of the synthesized molecules was confirmed by infrared spectroscopy, mass spectrometry, and both 1H and 13C NMR analyses. The antimicrobial activities of the synthesized derivatives were evaluated by determining their minimum inhibitory concentrations (MICs) against a panel of bacterial and fungal strains. The results revealed that methoxy- and nitro-substituted derivatives exhibited significant antibacterial activity against Escherichia coli and Pseudomonas aeruginosa, whereas chloro, hydroxy, and nitro functionalized compounds demonstrated notable antifungal activity against Aspergillus niger and Aspergillus clavatus. Furthermore, molecular docking studies were performed using AutoDock software to investigate the binding interactions of the synthesized compounds with Staphylococcus aureus dihydrofolate reductase (DHFR) in complex with trimethoprim. In addition, in silico ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analyses were carried out to assess the physicochemical properties, drug-likeness, and therapeutic potential of the developed compounds.