Bioactive Imine-Amoxicillin Hybrids: Dual Antibacterial and Anti-Breast Cancer Potentials Supported by Molecular Docking: Bioactive Imine-Amoxicillin Hybrids

Basma Bedair; Nada Bedair; Zeena Abdulameer; Zeena Salman

doi:10.29409/2vpat285

Authors

Basma H. Bedair Department of Experimental Therapy, Iraqi Center for Cancer Research and Medical Genetics Research, Mustansiriyah University, Baghdad, Iraq
Nada H. Bedair Department of Forensic Biology, Higher Institute of Forensic Science, Al-Nahrain University, Baghdad, Iraq
Zeena Ali Abdulameer Al-Turath University, Baghdad, Iraq.
Zeena Thamir Salman Scientific Research Commission, Baghdad, Iraq.

DOI:

https://doi.org/10.29409/2vpat285

Keywords:

Amoxicillin, Drug resistance, Imine, MCF-7

Abstract

Antimicrobial and anticancer drug resistance represent two of the main global challenges for public health and require immediate practical solutions. Drug-resistant cancer chemotherapy and the growing threat posed by antimicrobial-resistant infections represent additional biomedical challenges. Thus, one viable way forward to develop multifunctional candidates with improved biological value is by altering existing drugs through chemical modification. Three imine-amoxicillin hybrids, J1-J3, were synthesized from the condensation of amoxicillin trihydrate with 2,4-dihydroxy-3-propylbenzaldehyde, 3-ethyl-4-hydroxy-5-methylbenzaldehyde, and 2-(3-formyl-4-hydroxyphenyl)acetonitrile. All products were successfully obtained as yellow to yellowish-orange precipitates, and subsequent characterization of the products by FTIR demonstrated that azomethine C=N bands formed during the condensation reactions. FTIR data also revealed the formation of new azomethine bands corresponding to derivatives J1 at 1643, J2 at 1620, and J3 at 1644 cm^-1, indicating that Schiff base synthesis occurred. Additionally, docking studies were performed against the 6IIO protein, and the results revealed that synthesized derivatives J1, J2, and J3 possessed favorable docking scores of -7.83371, -8.18972, and -8.1703 kcal/mol, respectively. Derivatives J2 and J3 demonstrated the strongest antibacterial activity against S. pyogenes and B. subtilis, producing inhibition zones of 35 mm and 26 mm, respectively, at 0.1 mg/mL within the study. Furthermore, compared with the synthesized derivative J1, the synthesized derivative J3 exhibited stronger cytotoxic activity against the MCF-7 cell line, with IC50 values of 123.8 and 160.3 μg/mL, respectively. Finally, on the basis of ADMET prediction data, the gastrointestinal absorption of all three molecules is expected to be low, and only derivatives J3 and J2 will comply with the proposed rules of Lipinski’s rule.

Author Biographies

Basma H. Bedair, Department of Experimental Therapy, Iraqi Center for Cancer Research and Medical Genetics Research, Mustansiriyah University, Baghdad, Iraq

Assistant Lecturer at the Department of Experimental Therapy in the Iraqi Center for Cancer Research and Medical Genetics.
Nada H. Bedair, Department of Forensic Biology, Higher Institute of Forensic Science, Al-Nahrain University, Baghdad, Iraq

Assistant Lecturer at the Department of Forensic Biology, Higher Institute of Forensic Science, Al-Nahrain University, Baghdad, Iraq.
Zeena Ali Abdulameer, Al-Turath University, Baghdad, Iraq.

Assistant Lecturer at Al-Turath University, Baghdad, Iraq.
Zeena Thamir Salman, Scientific Research Commission, Baghdad, Iraq.

Assistant Lecturer at Scientific Research Commission, Baghdad, Iraq.

References

1. Howard, A., et al., Artificial intelligence and infectious diseases: tackling antimicrobial resistance, from personalised care to antibiotic discovery. The Lancet Infectious Diseases, 2026. 26(3): p. e181-e192.

2. Zhang, L., et al., Bacterial efflux pump inhibitors reduce antibiotic resistance. Pharmaceutics, 2024. 16(2): p. 170.

3. Faraj, R., et al., Novel 1, 3-oxazepine-4, 7-dione derivatives with antimicrobial anticancer and corrosion inhibition potential. Discover Chemistry, 2026. 3(1): p. 2.

4. Yusuf, K., V. Sampath, and S. Umar, Bacterial infections and cancer: exploring this association and its implications for cancer patients. International Journal of Molecular Sciences, 2023. 24(4): p. 3110.

5. Mahdi, A.A., et al., Investigation of some chemotherapy drugs induce cardiotoxicity. Al-Salam Journal for Medical Science, 2025. 4(2): p. 1-10.

6. Zhou, J., et al., The impact of antibiotic use on clinical features and survival outcomes of cancer patients treated with immune checkpoint inhibitors. Frontiers in immunology, 2022. 13: p. 968729.

7. Dhanda, G., Y. Acharya, and J. Haldar, Antibiotic adjuvants: a versatile approach to combat antibiotic resistance. ACS omega, 2023. 8(12): p. 10757-10783.

8. Garnier, A.-S., et al., Nephrotoxicity of amoxicillin and third-generation cephalosporins: an updated review. Drug Safety, 2023. 46(8): p. 715-724.

9. Banbela, H.M., et al., Amoxicillin antibiotic with potential anticancer and antidiabetic activity: acetaldehyde–amoxicillin Schiff base and its vanadyl complex with DFT and docking investigation. Materials Advances, 2025. 6(24): p. 9476-9494.

10. Ejaz, A., et al., Synthesis Characterization and Antimicrobial Investigation of Sulfonamide Derivatives of Transition Metal Complexes: A Review. Comments on Inorganic Chemistry, 2026. 46(3): p. 170-242.

11. Turos, E., N-Organothio β-Lactams Offer New Opportunities for Controlling Pathogenic Bacteria. Pathogens, 2025. 14(7): p. 628.

12. Islam, M., et al., Synthesis, characterization and antimicrobial studies of imine derivatives of amoxicillin. European Journal of Chemistry, 2015. 6(4): p. 417-421.

13. Oreshko, V.V., et al., Synthesis and antiviral properties of camphor-derived iminothiazolidine-4-ones and 2, 3-dihydrothiazoles. Molecules, 2022. 27(15): p. 4761.

14. Roney, M., et al., Polypharmacological assessment of Amoxicillin and its analogues against the bacterial DNA gyrase B using molecular docking, DFT and molecular dynamics simulation. Aspects of Molecular Medicine, 2023. 2: p. 100024.

15. Kobauri, P., et al., Rational design in photopharmacology with molecular photoswitches. Angewandte Chemie International Edition, 2023. 62(30): p. e202300681.

16. Babu, C.S. and C. Lim, Influence of solution ionic strength on the stabilities of M20 loop conformations in apo E. coli dihydrofolate reductase. The Journal of Chemical Physics, 2021. 154(19).

17. Wilhelm, A., et al., Synthesis, characterization and cytotoxic evaluation of chalcone derivatives. Journal of Molecular Structure, 2022. 1251: p. 132001.

18. DOKMAK, G.A.M., Synthesis, Characterization and In Vitro Kinetics of Amoxicillin and Cephalexin Antibacterial Prodrugs. 2014, AL-Quds University.

19. Chaudhary, N.K., Synthesis, Characterization and Biological Studies of 3d-Metal Complexes of Schiff Bases of Aminoglycosides and ß-Lactam Antibiotics. 2018, Faculty of Chemistry.

20. Yadav, L., Infrared (IR) spectroscopy, in Organic spectroscopy. 2005, Springer. p. 52-106.

21. Joksimović, N., et al., Multi-Target Anticancer Activity of Structurally Diverse Schiff Bases: Insights into Cell-Cycle Arrest, DNA Damage, Metabolic Signaling, and Biomolecular Binding. Current Issues in Molecular Biology, 2026. 48(1): p. 57.

22. Qiao, X., et al., Study on potential antitumor mechanism of a novel Schiff Base copper (II) complex: synthesis, crystal structure, DNA binding, cytotoxicity and apoptosis induction activity. Journal of inorganic biochemistry, 2011. 105(5): p. 728-737.

23. Abdel-Aziz, A.A.-M., et al., Antitumor activity and multi-target mechanism of phenolic schiff bases bearing methanesulfonamide fragments: cell cycle analysis and a molecular modeling study. International Journal of Molecular Sciences, 2024. 25(24): p. 13621.

24. Scotti, C. and J.W. Barlow, Natural products containing the nitrile functional group and their biological activities. Natural Product Communications, 2022. 17(5): p. 1934578X221099973.

25. Mosam, R.A., Biodetoxification of Organic Contaminants Using Microorganisms Isolated from Gold (Au) Mine Tailings. 2022, University of South Africa (South Africa).

26. Yao, D., L. Xia, and G. Li, Research progress on the application of covalent organic framework nanozymes in analytical chemistry. Biosensors, 2024. 14(4): p. 163.

Bioactive Imine-Amoxicillin Hybrids: Dual Antibacterial and Anti-Breast Cancer Potentials Supported by Molecular Docking