Synthesis of N-Methylene Linker Containing Phthalimide Bearing-1H-1,2,3-Triazole by Click Chemistry Approach: Anticancer Activity in Human Cells

Abstract

The novel series of phthalimide-1H-1,2,3-triazole derivatives (6a–o) was created by combining various azide derivatives with an N-methylene bond using click chemistry. N-alkylation procedures using a base catalyst were used to make the initial alkyne. ¹H NMR, ¹³C NMR, IR, mass spectrometry, and elemental analysis methods were used to comprehensively characterize all intermediates and final products. The antitumor efficacy of reported hybrids of two heterocyclic rings, phthalimide and 1,2,3-triazole in a single structure, was tested against nine basic cancer panels as well as the NCI-60 cell line. The compounds 6a, 6b, 6e, 6g, 6h, and 6j showed potent anticancer activity in vitro against Leukemia, non-small cell lung cancer, renal cancer, and melanoma cancer cell lines, with GI₅₀ values ranging from −61.57 to 12.07 µM. The antimicrobial activity of fractions was tested. Further to gain an insight into the mechanism of action molecular docking study was performed against Epidermal Growth Factor Receptor Tyrosine Kinase which could provide valuable insights into the key thermodynamic interactions.

Keywords:

• Anticancer screening
• antimicrobial activity
• click chemistry
• molecular docking
• NCI-60 cell lines

Acknowledgments

We are thankful to the Department of Chemistry, Saurashtra University, Rajkot for their great support in the laboratory and library facility. The authors are also thankful to the Center of Excellence, NFDD Complex, Rajkot, for instrument facilities. Special thanks to the National Cancer Institute/National Institute of Health (NCI-NIH) in the United States for anticancer testing of synthesized molecules, as well as CO-ADD (The Community for Antimicrobial Drug Discovery) in the United Kingdom and The University of Queensland in Australia for rapid antimicrobial screening. The authors are also thankful to Schrödinger Inc. for providing the Small-Molecule Drug Discovery Suite (2018) to carry out the molecular docking studies.

Disclosure statement

No potential conflict of interest was reported by the author(s).