Synthesis and Biological Evaluation of Novel N-[3-fluoro-4-(morpholin-4-yl)phenyl]thiazol-2-amine Derivatives as Potent Antibacterial and Anticancer Agents and ADMET

In search of better antibacterial and anticancer agents, this report presents a series of novel N-[3-fluoro-4-(morpholin-4-yl)aryl]thiazol-2-amine derivatives (6a-6l) that were synthesized and evaluated for their antibacterial and anticancer activity in vitro. Antibacterial activity against three G(+) bacterial strains and anticancer activity against MCF-7 and A-549 was evaluated. Among all the tested compounds, 6i and 6j exhibited potent antibacterial activity against Staphylococcus aureus and Staphylococcus epidermidis bacterial strains. Biofilm profiles for the potent compounds and it was observed from the results that the active derivatives 6i and 6j were not only potent antibacterial agents but also efficient inhibitors of S. aureus and S. epidermidis biofilm growth. Compared to the standard drug, erlotinib, the anticancer activity screening results of 6h and 6k demonstrated high cytotoxic activity against the A-549 cancer cell line. Later, the results of the inhibitory assay of potent compounds 6h and 6k against the tyrosine kinase EGFR revealed that compound 6k showed approximate to 1.5 fold potency of the reference drug erlotinib. Finally, compounds 6h, 6i, 6j, and 6k did not show AMES toxicity and followed the rules of Lipinski, Ghose, Veber, Egan, and Muegge rules without any deviation.

Automated summary

This report presents a series of novel N-[3-fluoro-4-(morpholin-4-yl)aryl]thiazol-2-amine derivatives (6a-6l) that were synthesized and evaluated for their antibacterial and anticancer activity. Among them, compounds 6i and 6j exhibited potent antibacterial activity against Staphylococcus aureus and Staphylococcus epidermidis, and also demonstrated inhibitory effects on biofilm growth. Compounds 6h and 6k showed high anticancer activity against the A-549 cancer cell line, with compound 6k exhibiting similar potency to the reference drug erlotinib against EGFR.