Synthesis, characterization, and anticancer activity of Schiff bases

Abstract

Five Schiff bases, 2-((3-chlorophenylimino)methyl)-5-(diethylamino)phenol (L1), 2-((2,4-dichlorophenylimino)methyl)-5-(diethylamino)phenol (L2), 5-(diethylamino)-2-((3,5-dimethylphenylimino)methyl)phenol (L3), 2-((2-chloro-4-methylphenylimino)methyl)-5-(diethylamino)phenol (L4), and 5-(diethylamino)-2-((2,6-diethylphenylimino)methyl)phenol (L5) were synthesized and characterized by elemental analysis, FT-IR, ¹H and ¹³C NMR spectroscopy. Three of the compounds (L1, L2, and L4) were analyzed by single crystal X-ray diffraction: L1 and L2 crystallized in orthorhombic P2₁2₁2₁ and Pca2₁ space group, respectively, while L4 crystallized in monoclinic P2₁/c space group. Theoretical investigations were performed for all the synthesized compounds to evaluate the structural details. Drug–DNA interaction studies results from UV–Vis spectroscopy and electrochemistry complement that the compounds bind to DNA through electrostatic interactions. The cytotoxicity of the synthesized compounds was studied against cancer cell lines (HeLa and MCF-7) and a normal cell line (BHK-21) by means of an MTT assay compared to carboplatin, featuring IC₅₀ values in the micromolar range. The pro-apoptotic mechanism for the active compound L5 was evaluated by fluorescence microscopy, cell cycle analysis, caspase-9 and -3 activity, reactive oxygen species production, and DNA binding studies that further strengthen the results of that L5 is a potent drug against cancer.

Communicated by Ramaswamy H. Sarma

Keywords:

• Schiff base
• DFT
• electrochemistry
• DNA interaction studies
• antitumor activity

Disclosure statement

No potential conflict of interest was reported by the authors.