Nitrile-containing copper(ii) porphyrin coordination complexes for efficient anticancer activity and mechanism research

Abstract

Nitrile-functionalized anticancer drugs have drawn wide attention. However, the water solubility and side-effects of the drugs reduce their effectiveness in cancer therapy. In this paper, three novel para-, meta- and ortho-linked nitrile-containing water solubility copper(II) porphyrin complexes have been synthesized. Then the relationship between the structure and anticancer performance of the three complexes were investigated. When the complexes have an effect on the cancer cells (A549, H1975, HepG2 and T47D) and normal cell (Hs578 Bst), they demonstrate effective anticancer activity and biocompatibility; the para-nitrile functionalized complex p-CuP can selectively act on H1975 cells, with the lowest IC₅₀ (6.09 μM); the anticancer effect of water-soluble porphyrin ligands (p-L, m-L and o-L) is augmented by coordinate to copper ion(II). Furthermore, DNA binding and flow cytometry methods were applied to research their mechanism, and the results show that these complexes could intercalate DNA and the effect of p-CuP is the best, so there is DNA binding in the anticancer mechanism, also accompanied by mitochondrial dysfunction and arresting cell cycle. In addition, Density Functional Theory (DFT) calculation analyses were carried out for the cationic porphyrin ligands and complexes, using the method with a B3LYP level of theory with the 6-31G(d) and LanL2DZ basis sets, which further proved the biological activities of the target compounds.