Structure-based computational analysis of Tetrazoloquinoline-thiazolidinedione conjugates against bacterial and fungal targets.

Increasing resistance in bacterial and fungal pathogens to currently available antimicrobial agents highlights the need for the development of new antimicrobial agents. Recently, Tetrazoloquinoline and thiazolidinedione analogues have been considered interesting heterocyclic moieties due to their potential activity against microbial infections. This study focused on identifying novel Tetrazoloquinoline-thiazolidinedione conjugates as potent antibacterial and antifungal agents using computational tools, including molecular docking, DFT, molecular dynamics simulation, and in silico ADMET analysis. The molecular docking studies showed that the studied compounds have good binding affinities and interactions with the target proteins 4DUH (-10.6 to -9.8 kcal/mol) and 2AIB (-12.4 to -11.0 kcal/mol). Of all, the trifluoromethyl-substituted compounds AS-56 and AS-296 have a strong affinity. Furthermore, DFT analysis indicated the ideal structural properties, while 100 ns molecular dynamics simulation analysis was performed to follow the behaviour of the complexes formed between the ligands and the target proteins to evaluate their stability over time. The results indicate that AS-56 and AS-296 have a stable conformation and binding patterns in a stimulating environment of the protein-ligand complexes. ADME analysis predicted that the compounds (AS-56, AS-16, and AS-68) have good oral bioavailability and pharmacokinetics. The toxicity profile examination of the compounds predicted acceptable toxicity for these lead compounds.