Biomolecular Interaction, Anti-Cancer and Anti-Angiogenic Properties of Cobalt(III) Schiff Base Complexes

Subramanian Ambika,Mohammad Abdulkader Akbarsha,Ponnambalam Venuvanalingam,Sankaralingam Arunachalam,Rajadurai Vijay Solomon,Muthuraman Sundararaman,Balakrishnan Gowdhami,Kishore Kumar Meenakshi Sundaram,Yesaiyan Manojkumar

doi:10.1038/s41598-019-39179-1

Abstract

Two cobalt(III) Schiff base complexes, trans-[Co(salen)(DA)2](ClO4) (1) and trans-[Co(salophen)(DA)2](ClO4) (2) (where salen: N,N’-bis(salicylidene)ethylenediamine, salopen: N,N’-bis(salicylidene)-1,2-phenylenediamine, DA: dodecylamine) were synthesised and characterised using various spectroscopic and analytical techniques. The binding affinity of both the complexes with CT-DNA was explored adopting UV-visible, fluorescence, circular dichroism spectroscopy and cyclic voltammetry techniques. The results revealed that both the complexes interacted with DNA via intercalation as well as notable groove binding. Protein (BSA) binding ability of these complexes was investigated by absorption and emission spectroscopy which indicate that these complexes engage in strong hydrophobic interaction with BSA. The mode of interaction between these complexes and CT-DNA/BSA was studied by molecular docking analysis. The in vitro cytotoxic property of the complexes was evaluated in A549 (human small cell lung carcinoma) and VERO (African green monkey kidney cells). The results revealed that the complexes affect viability of the cells. AO and EB staining and cell cycle analysis revealed that the mode of cell death is apoptosis. Both the complexes showed profound inhibition of angiogenesis as revealed in in-vivo chicken chorioallantoic membrane (CAM) assay. Of the two complexes, the complex 2 proved to be much more efficient in affecting the viability of lung cancer cells than complex 1. These results indicate that the cobalt(III) Schiff base complexes in this study can be potentially used for cancer chemotherapy and as inhibitor of angiogenesis, in general, and lung cancer in particular, for which there is need for substantiation at the level of signalling mechanisms and gene expressions.

Highlights

IntroductionCobalt complexes containing Schiff base ligands have been shown to possess more efficient anti-cancer activity against cancer cells such as MCF-7, A431 and HeLa than cis-platin[9,10,11]
Some fluorine-substituted iron(III) salophen complexes are found to be highly cytotoxic to HT-29, MCF-7 and MDA-MB-231 cells[16]
Bovine serum albumin (BSA) is mainly due to hydrophobic forces

Summary

Introduction

Cobalt complexes containing Schiff base ligands have been shown to possess more efficient anti-cancer activity against cancer cells such as MCF-7, A431 and HeLa than cis-platin[9,10,11]. Metal complexes containing tetradentate Schiff bases, salen and salophen, show a broad spectrum of biological activities, in the context of cancer[12,13,14,15]. Some methoxy group-substituted salophen containing iron(III) complexes are very active against cis-platin-resistant cancer cell lines[17]. The methoxy substituent was equipotent to cis-platin, but hydroxy-substituted complexes did not show significant cytotoxic activity in cancer cells. The above background information encouraged us to synthesize long alkyl chain-containing cobalt(III) salen/salophen Schiff base complexes and study their bio-molecular interaction adopting both experimental and theoretical approaches. The anti-cancer and anti-angiogenic potentials of the complexes have been investigated

Methods

Results

Conclusion