Lamotrigine derivatives-synthesis, anti-cancer, and anti-MDR-bacterial activities

Khan M. K., Siddiqui H., Sharif R., GÜZEL M., Wahab A., Yousuf S., ...More

Journal of Molecular Structure, vol.1264, 2022 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 1264
  • Publication Date: 2022
  • Doi Number: 10.1016/j.molstruc.2022.133277
  • Journal Name: Journal of Molecular Structure
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, INSPEC
  • Keywords: Lamotrigine, Quaternary ammonium salts, Anti-bacterial activity, Staphylococcus aureus, Cancer cell lines, Cytotoxicity, HeLa, Breast cancer, MCF-7, MDA-MB
  • Istanbul Medipol University Affiliated: Yes

Abstract

A new series of quaternary ammonium salts 3–21 of lamotrigine (6-(2, 3-dichlorophenyl)-1, 2, 4-triazine-3, 5-diamine) was synthesized via N-alkylation of lamotrigine using different benzyl bromides. The new analogues were characterized by using FT-IR, NMR, and mass spectrometric techniques. Single-crystal X-ray diffraction analysis of compound 10 was also carried out to confirm the position of substitution and salt formation. All the compounds 3-21 were tested for various biological activities, including anti-bacterial, and anti-cancer properties. All compounds, except 20, exhibited a potent growth inhibition of Staphylococcus aureus strains as compared to the ofloxacin, the standard drug. Compounds 4, 7, 10, and 13 showed a significant toxicity towards HeLa cell line (derived from cervical carcinoma), whereas compounds 3, and 5 showed a significant activity towards HeLa, MCF-7 (estrogen and progesterone positive breast cancer cell line), and MDA-MB cell lines (epithelial, human breast cancer cell line), as compared to the standard drug doxorubicin. To the best of our knowledge all analogues of 6-(2, 3-dichlorophenyl)-1, 2, 4-triazine-3, 5-diamine, and their activity against MDR, and anti-cancer is reported here for the first time.