Zinc(II) Terpyridine Complexes: Substituent Effect on Photoluminescence, Antiproliferative Activity, and DNA Interaction.

Jiahe Li,Zhen Ma,Hailan Chen,Gang Huang,Ling Huang,Lixia Pan,Jinzhang Jiang,Rongping Liu,Xing Liang

doi:10.3390/molecules24244519

Abstract

A series of ZnCl2 complexes (compounds 1–10) with 4′-(substituted-phenyl)-2,2′:6′,2′′-terpyridine that bears hydrogen (L1), p-methyl (L2), p-methoxy (L3), p-phenyl (L4), p-tolyl (L5), p-hydroxyl (L6), m-hydroxyl (L7), o-hydroxyl (L8), p-carboxyl (L9), or p-methylsulfonyl (L10) were prepared and then characterized by 1H NMR, electrospray mass-spectra (ESI-MS), IR, elemental analysis, and single crystal X-ray diffraction. In vitro cytotoxicity assay was used to monitor the antiproliferative activities against tumor cells. Absorption spectroscopy, fluorescence titration, circular dichroism spectroscopy, and molecular modeling studied the DNA interactions. All of the compounds display interesting photoluminescent properties and different maximal emission peaks due to the difference of the substituent groups. The cell viability studies indicate that the compounds have excellent antiproliferative activity against four human carcinoma cell lines, A549, Bel-7402, MCF-7, and Eca-109, with the lowest IC50 values of 0.33 (10), 0.66 (6), 0.37 (7), and 1.05 (7) μM, respectively. The spectrophotometric results reveal that the compounds have strong affinity binding with DNA as intercalator and induce DNA conformational transition. Molecular docking studies indicate that the binding is contributed by the π…π stacking and hydrogen bonds, providing an order of nucleotide sequence binding selectivity as ATGC > ATAT > GCGC. These compounds intercalate into the base pairs of the DNA of the tumor cells to affect their replication and transcription, and the process is supposed to play an important role in the anticancer mechanism.

Highlights

Cancer is the second leading cause of global death and it is responsible for an estimated 9.6 million loss of human lives in 2018
The results of electronic absorption, fluorescence titration, and circular dichroism spectroscopy show that the ten compounds have strong affinity to bind with DNA
The Circular Dichroism (CD) spectra show that the secondary structure of DNA is changed by the addition of the compounds, which results in the DNA conformational transition

Summary

Introduction

Cancer is the second leading cause of global death and it is responsible for an estimated 9.6 million loss of human lives in 2018. The Pt-based drugs, such as cisplatin and carboplatin, are widely used as anticancer agents. These platinum complexes display severe side effects, such as nephrotoxicity, neurotoxicity, and ototoxicity, which limit their applications [1,2,3,4]. Molecules can interact with DNA to affect its replication and transcription, leading to cell death and Molecules 2019, 24, 4519; doi:10.3390/molecules24244519 www.mdpi.com/journal/molecules. The development of metal complexes that have DNA sequence-selective and cleavage potential is essential for further expected applications in molecular biology, medicine, and related fields [20,21]

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