Design and synthesis of novel pyrrole coupled tryptamine derivatives as contenders against Staphylococcus aureus

Twenty-four new hybrid Pyrrole-tryptamines compounds were synthesized and thoroughly characterized using various techniques such as FT-IR, 1H NMR, 13C NMR, and LC-MS. An evaluation of each compound was conducted based on criteria including their PASS, BBB, ADME, pharmacophore model, and bioactive score. Antibacterial testing of all derivatives indicated that compound 5j exhibited strong activity against MRSA. Investigations into membrane damage, supported by SEM images, cellular content leakage, potassium efflux, and changes in lipid profiles, confirmed the anti-MRSA properties of compound 5j. In an in silico molecular docking analysis, compound 5j achieved a binding score of − 10.02 against the MRSA protein 6FTB, while streptomycin scored − 10.25. Additionally, when compared to standard doxorubicin against 3T3L1 cell lines, compound 5j demonstrated a less toxic IC50 effect of 669.80 µM on normal cell lines. These findings warrant further research on compound 5j for the potential development of a medication to treat MRSA infections.