A New Concept of Enhancing the Anticancer Activity of Manganese Terpyridine Complex by Oxygen-Containing Substituent Modification

Abstract

Eleven manganese 4′-substituted-2,2′:6′,2″-terpyridine complexes (1a–1c and 2a–2h) with three non-oxygen-containing substituents (L1a–L1c: phenyl, naphthalen-2-yl and naphthalen-1-yl, L1a–L1c) and eight oxygen-containing substituents (L2a–L2h: 4-hydroxyl-phenyl, 3-hydroxyl-phenyl, 2-hydroxyl-phenyl, 4-methoxyl-phenyl, 4-carboxyl-phenyl, 4-(methylsulfonyl)phenyl, 4-nitrophenyl and furan-2-yl) were prepared and characterized by IR, elemental analysis or single crystal X-ray diffraction. In vitro data demonstrate that all of these show higher antiproliferative activities than cisplatin against five human carcinoma cell lines: A549, Bel-7402, Eca-109, HeLa and MCF-7. Compound 2d presents the strongest antiproliferative effect against A549 and HeLa cells, with IC50 values being 0.281 μM and 0.356 μM, respectively. The lowest IC50 values against Bel-7402 (0.523 μM) Eca-109 (0.514 μM) and MCF-7 (0.356 μM) were obtained for compounds 2h, 2g and 2c, respectively. Compound 2g with a nitro group showed the best results on the whole, with relevantly low IC50 values against all the tested tumor cells. The DNA interactions with these compounds were studied by circular dichroism spectroscopic and molecular modeling methods. Spectrophotometric results revealed that the compounds have strong affinities in binding with DNA as intercalators, and the binding induces DNA conformational transition. Molecular docking studies indicate that the binding is contributed by the π–π stacking and hydrogen bonds. The anticancer activities of the compounds are correlated with their DNA binding ability, and the modification of oxygen-containing substituents significantly enhanced the anticancer activity, which could provide a new rationale for the future design of terpyridine-based metal complexes with antitumor potential.

Cobalt (II), Nickel (II) and Palladium (II) complexes appended terpyridine‐based ligand: Synthesis, spectral characterization, anticancer activity and apoptosis investigation

“…Copper (II) and Zinc (II) terpyridine conjugated complexes prepared by Velugula et al induced apoptosis in MCF‐7 and HeLa cells, whose activities were comparable with cisplatin 16 . Manganese complexes with terpyridine ligands acted as DNA intercalators, which coincided with their anticancer activity on MCF‐7, Bel‐7402, A549, Eca‐109, and HeLa cells 21 . Our research group has also reported potential anticancer activity of cobalt (III) bitpy complex against MCF‐7 and HeLa cells 22 .…”

“…16 Manganese complexes with terpyridine ligands acted as DNA intercalators, which coincided with their anticancer activity on MCF-7, Bel-7402, A549, Eca-109, and HeLa cells. 21 Our research group has also reported potential anticancer activity of cobalt (III) bitpy complex against MCF-7 and HeLa cells. 22 Albeit numerous terpyridine complexes have shown good activity against cancer cells, the factors that oversee their action and target are still obscure.…”