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

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. H-1 NMR, C-13 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 GI(50) values ranging from -61.57 to 12.07 mu M. 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.

Automated summary

The novel series of phthalimide-1H-1,2,3-triazole derivatives synthesized in this study showed potent anticancer activity against leukemia, non-small cell lung cancer, renal cancer, and melanoma cancer cell lines. The compounds were comprehensively characterized and their antimicrobial activity was also tested. Molecular docking studies provided insights into the mechanism of action.