Novel tetrahydronaphthalen-1-yl-phenethyl ureas: synthesis and dual antibacterial-anticancer activities

Abstract

Cancer and antibiotic-resistant bacterial infections are significant global health challenges. The resistance developed in cancer treatments intensifies therapeutic difficulties. In addressing these challenges, this study synthesised a series of N,N′-dialkyl urea derivatives containing methoxy substituents on phenethylamines. Using isocyanate for the efficient synthesis yielded target products 14–18 in 73–76% returns. Subsequently, their antibacterial and anticancer potentials were assessed. Cytotoxicity tests on cancer cell lines, bacterial strains, and a healthy fibroblast line revealed promising outcomes. All derivatives demonstrated robust antibacterial activity, with MIC values ranging from 0.97 to 15.82 µM. Notably, compounds 14 and 16 were particularly effective against the HeLa cell line, while compounds 14, 15, and 17 showed significant activity against the SH-SY5Y cell line. Importantly, these compounds had reduced toxicity to healthy fibroblast cells than to cancer cells, suggesting their potential as dual-functioning agents targeting both cancer and bacterial infections.

Graphical Abstract

Keywords:

• Antibacterial activity
• anticancer activity
• isocyanates
• N,N′-dialkyl urea
• phenethylamine

Acknowledgements

The authors would like to thank The Knut and Alice Wallenberg Foundation.

Author contributions

Conceptualisation, Y.A., A.M., and F.N.K.; methodology, Y.A. and F.N.K.; software, M.E.A.; validation, M.E.A., S.G., and H.T.; formal analysis, S.G.; investigation, H.T.; resources, A.M.; data curation, S.G.; writing – original draft preparation, Y.A. and M.E.A.; writing – review and editing, F.N.K. and Y.A.; visualisation, F.N.K.; supervision, H.T.; project administration, Y.A.; funding acquisition, S.G. All authors have read and agreed to the published version of the manuscript.

Disclosure statement

The authors declare no conflict of interest.

Data availability statement

The data presented in this study are available on request from the corresponding author. The data are not publicly available due to privacy.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.