N,N-Bis(Substituted benzyl)-β-Carbolineum Bromides as Potential Anticancer Therapeutics: Design, Synthesis, Cytotoxicity, Drug-DNA Intercalation and In-Silico Binding Properties

Mohideen, Mazlin; Kamaruzaman, Nur Azzalia; Hamali, Muhamad Azwan; Mordi, Mohd Nizam; Mansor, Sharif Mahsufi; Rahman, A. F. M. Motiur

doi:10.1016/j.molstruc.2021.130771

Cited by 3 publications

(2 citation statements)

References 45 publications

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“…11g (0.72 μM) was the most potent against the K562 cancer cell line, as given in Figure 9. DNA intercalation for 11g was carried out by UV-vis spectroscopy with K b value 2.67 × 10 4 M −1 and molecular docking by Auto Dock 4.2 with docking score − 10.65 suggest intercalation by π-π stacking interaction between base pairs (Mohideen et al, 2021).…”

Section: Miscellaneousmentioning

confidence: 99%

DNA intercalators as anticancer agents

et al. 2022

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Cancer is one of the most prevailing disease conditions, which occurs due to uncontrolled cell division either due to natural mutation to the genes or due to changes induced by physical, chemical, or biological carcinogens. According to WHO, it is the second leading cause of death worldwide and has reported 10 million deaths in 2020. Hence, there arises the need for better chemotherapies and DNA intercalators are one such emerging therapy for cancer. DNA intercalating agents reversibly intercalate with the double‐helical structure of DNA by interacting with adjacent base pairs and disrupting the structure of DNA and thereby causing cell death. Here, we discuss the different classes of organo‐intercalators used in cancer therapy describing their anticancer and intercalation ability by different methods along with their structure–activity relationship and mechanism of action.

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Section: Miscellaneousmentioning

confidence: 99%

DNA intercalators as anticancer agents

et al. 2022

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“…Copper(II) complexes can identify DNA via non-covalent binding modes such as intercalation, groove, and external electrostatic contacts, leading to significant distortion in its structure and the proper biological function [20,21]. Intercalative binding, which is facilitated through welltailored aromatic structures able to stabilize the π-π interactions, is considered to be the most effective mode for DNA targeting drugs [22,23]. At the same time, in copper(II) complexes, the number of single ligands acts in a bidentate manner in combination with a fourth monodentate labile one, which enables the complex to covalently bind with the nucleobases or the phosphate backbone or other interactions with cellular targets, thereby exerting their cytotoxicity [24,25].…”

Section: Introductionmentioning

confidence: 99%

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

Alolayqi¹,

Afzal²,

Alarifi³

et al. 2021

Crystals

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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.

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