Abstract
Background: Cell inhibitors are gradually becoming a tool in drug discovery as this gives a lead to potential compounds with therapeutic application. Presently, cancer cell inhibitors have shown drug-likeness based on oral bioavailability, pharmacokinetics, global chemical reactivity and theoretical binding affinities. Herein, we report copper complexes synthesized from aminobenzoic acid moiety, 3-(2-hydroxybenzylideneamino) benzoic acid copper complex and 4-(2-hydroxybenzylideneamino) benzoic acid copper complex as potential cell inhibitors of cyclin-dependent kinase 7.
Methods: The complexes were synthesized by condensation of 2-hydroxybenzylideneamino benzoic acid moiety Schiff bases with copper(II) chloride and characterized using Fourier Transform Infrared Spectroscopy, Electrospray ionization mass spectrometry, and ultraviolet-vis spectroscopy. The complexes were optimized using the M062X functional and GENECP basis set. DNA study was carried out on calf thymus DNA using circular dichroism. Human cyclin-dependent kinase 7 was processed using BIOVIA Discovery Studio 2020, docking simulations were conducted utilizing PyrxAutoDock. Independent runs at complex binding sites were assessed and ranked utilizing the Vina scoring function.
Results: The planar geometry of the complexes was validated by Density Functional Theory calculations. Results of analysis showed that both copper complexes are less toxic and exhibited higher binding energies to amino acid residues of cyclin-dependent kinase 7 when compared with all reference drugs, Epirubicin, Capecitabine, and 5-Fluorouracil. DNA study revealed minor groove binding to copper complexes via hydrogen bonding and validated by molecular docking.
Conclusion: 3-(2-hydroxybenzylideneamino) benzoic acid copper complex and 4-(2-hydroxybenzylideneamino) benzoic acid copper complex has shown potential activities that can inhibit cyclin-dependent kinase 7 in cancer therapy.
Keywords: Cancer; DFT calculations; DNA binding; molecular docking; synthesis.
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