Depicting the DNA Binding and Cytotoxicity Studies against Human Colorectal Cancer of Aquabis (1-Formyl-2-Naphtholato-k2O,O′) Copper(II): A Biophysical and Molecular Docking Perspective

Ebtisam Alolayqi,Abeer Beagan,Abdullah Alarifi,Mohd Muddassir,Mohd Afzal

doi:10.3390/cryst12010015

Abstract

In this study, we attempted to examine the biological activity of the copper(II)–based small molecule aquabis (1-formyl-2-naphtholato-k2O,O′)copper(II) (1) against colon cancer. The characterization of complex 1 was established by analytical and spectral methods in accordance with the single-crystal X-ray results. A monomeric unit of complex 1 exists in an O4 (H2O) coordination environment with slightly distorted square pyramidal geometry (τ = ~0.1). The interaction of complex 1 with calf thymus DNA (ctDNA) was determined by employing various biophysical techniques, which revealed that complex 1 binds to ctDNA at the minor groove with a binding constant of 2.38 × 105 M–1. The cytotoxicity of complex 1 towards human colorectal cell line (HCT116) was evaluated by the MTT assay, which showed an IC50 value of 11.6 μM after treatment with complex 1 for 24 h. Furthermore, the apoptotic effect induced by complex 1 was validated by DNA fragmentation pattern, which clarified that apoptosis might be regulated through the mitochondrial-mediated production of reactive oxygen species (ROS) causing DNA damage pathway. Additionally, molecular docking was also carried out to confirm the recognition of complex 1 at the minor groove.

Highlights

Regardless of the significant advancement in the treatment of colon cancer, its frequency is steadily rising, and it has become one of the leading causes of death worldwide [1,2,3]
Apart from conventional chemotherapy based on organic and platinum-based drugs, other treatment regimes such as surgery, radiation, and immunotherapy therapy are available to treat colon cancer [5,6,7,8]
A remarkable study on small molecules binding with nucleic acids (DNA and RNA), which displayed significant impression owing to their vital roles in molecular biology, was carried out [9,10,11]

Summary

Introduction

Regardless of the significant advancement in the treatment of colon cancer, its frequency is steadily rising, and it has become one of the leading causes of death worldwide [1,2,3]. Metal-based enzyme and protein inhibition plays a crucial role in metabolic pathways associated with cancer, which present common targets for the design of metal-based drugs [14,15]. Literature reports revealed that DNA remains a versatile target for metal-based therapeutic agents, and it has been examined by several factors in terms of the coordination environment and the nature of the organic frameworks [16,17]. Of all the transition metal complexes, the Cu(II) metal ion is the most widely studied and known to play a significant role in cancer research because some genetic pathways require a higher level of copper during cancer progression than can be found in normal tissues [18,19]

Methods

Results

Conclusion