Biological evaluation of dinuclear copper complex/dichloroacetic acid cocrystal against human breast cancer: design, synthesis, characterization, DFT studies and cytotoxicity assays

Usman, Mohammad; Arjmand, Farukh; Khan, Rais Ahmad; Alsalme, Ali; Ahmad, Musheer; Tabassum, Sartaj

doi:10.1039/c7ra08262b

Cited by 39 publications

(15 citation statements)

References 90 publications

(65 reference statements)

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“…The standard protocol [ 32 ] was adopted for both the experiments, with the slight modifications that we reported earlier [ 36 , 37 , 38 , 39 , 40 ].…”

Section: Methodsmentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of Benzimidazole-Derived Biocompatible Copper(II) and Zinc(II) Complexes as Anticancer Chemotherapeutics

Alajmi

Hussain

Rehman

et al. 2018

IJMS

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Herein, we have synthesized and characterized a new benzimidazole-derived “BnI” ligand and its copper(II) complex, [Cu(BnI)2], 1, and zinc(II) complex, [Zn(BnI)2], 2, using elemental analysis and various spectroscopic techniques. Interaction of complexes 1 and 2 with the biomolecules viz. HSA (human serum albumin) and DNA were studied using absorption titration, fluorescence techniques, and in silico molecular docking studies. The results exhibited the significant binding propensity of both complexes 1 and 2, but complex 1 showed more avid binding to HSA and DNA. Also, the nuclease activity of 1 and 2 was analyzed for pBR322 DNA, and the results obtained confirmed the potential of the complexes to cleave DNA. Moreover, the mechanistic pathway was studied in the presence of various radical scavengers, which revealed that ROS (reactive oxygen species) are responsible for the nuclease activity in complex 1, whereas in complex 2, the possibility of hydrolytic cleavage also exists. Furthermore, the cytotoxicity of the ligand and complexes 1 and 2 were studied on a panel of five different human cancer cells, namely: HepG2, SK-MEL-1, HT018, HeLa, and MDA-MB 231, and compared with the standard drug, cisplatin. The results are quite promising against MDA-MB 231 (breast cancer cell line of 1), with an IC50 value that is nearly the same as the standard drug. Apoptosis was induced by complex 1 on MDA-MB 231 cells predominantly as studied by flow cytometry (FACS). The adhesion and migration of cancer cells were also examined upon treatment of complexes 1 and 2. Furthermore, the in vivo chronic toxicity profile of complexes 1 and 2 was also studied on all of the major organs of the mice, and found them to be less toxic. Thus, the results warrant further investigations of complex 1.

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“…The standard protocol [ 32 ] was adopted for both the experiments, with the slight modifications that we reported earlier [ 36 , 37 , 38 , 39 , 40 ].…”

Section: Methodsmentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of Benzimidazole-Derived Biocompatible Copper(II) and Zinc(II) Complexes as Anticancer Chemotherapeutics

Alajmi

Hussain

Rehman

et al. 2018

IJMS

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“…MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay was carried out as described previously . The L and complexes 1–3 (0 – 300 μM), in DMSO were added to the wells containing 1 × 10 4 cells per well in 200 μL of fresh culture medium after their seeding for 24 hr.…”

Section: Methodsmentioning

confidence: 99%

Bioactive mono/bis (carboxyamide) based Co (II), Ni (II) and Cu (II) complexes: Synthesis, Characterization, DNA binding and Anticancer Potentials

Dhivya

Kathiresan

Vigneshwar

et al. 2018

Applied Organom Chemis

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Bioactive carboxyamide ligated Cu II (1), Co II (2) and Ni II (3) complexes have been synthesized and characterized using various physico-chemical techniques. In particular, the occurred slightly distorted square planar geometry in complex 1 was confirmed by single X-ray crystal structure. Their (1, 2 and 3) potential interactions with herring sperm DNA (HS-DNA) have been investigated using spectral and electrochemical techniques. All these studies suggested that the complex 1 could partially penetrated in the sugar phosphate backbone and stacked in between the DNA base pairs, while the other complexes 2 & 3 could bound only on the grooves of HS-DNA due to their bi-ligated architecture around the metal centre. The potent cytotoxicity of L and its complexes 1-3 was also evaluated against AGS human gastric cancer cells. Hoechst 33342/PI double staining images revealed that the complexes significantly induced cell death through apoptosis. In vivo administration of complex 1 remarkably inhibits the tumor growth in male Swiss albino mice, moreover it did not show any hepatotoxicity in mice. All these observed results suggested that these complexes may utilized as good conventional therapeutic agents in the near feature after a series of biological assessments.

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“…410-420 nm (λ em ). [43] The incremental addition of ct-DNA/tRNA (0-3.00 × 10 À 5 M) resulted in a slow increase in florescence intensity, with no shift in emission maxima (Figure S7). The resulting increase in fluorescence intensity could be attributed to the incorporation of complex 1 within the base stack of the ct-DNA/tRNA helix.…”

Section: Absorption Titration Studiesmentioning

confidence: 97%

Chromone‐Appended Zn(II) tRNA‐Targeted Potential Anticancer Chemotherapeutic Agent: Structural Details, in vitro ct‐DNA/tRNA Binding, Cytotoxicity Studies And Antioxidant Activity

et al. 2022

Self Cite

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A 3-formyl-chromone-appended zinc(II) intercalator drug candidate of the formulation [bis(chromone)(H 2 O) 2 Zn(II)] was prepared as a potent anticancer agent and thoroughly characterized by multi-spectroscopic and single X-ray crystallographic studies. Preliminary binding studies of complex 1 with ct-DNA/tRNA were carried out employing various complementary biophysical techniques and the corroborative results of these experiments suggested strong binding propensity via intercalation binding mode towards ct-DNA/tRNA therapeutic targets, with higher preference for tRNA as quantified by binding constant { K b , K and K sv } parameters. The cleavage studies with pBR322 DNA were performed which implied that 1 cleaved the DNA by hydrolytic cleavage pathway which was further validated by T4 religation assay. Moreover, 1 was found to exhibit the tRNA cleavage behavior in a concentration and time-dependent manner. The cytotoxicity of complex 1 was evaluated against Huh-7, DU-145 and the PNT2 cell lines by MTT assay. A dose-dependent growth inhibition of the Huh-7 and DU-145 cells at low micromolar concentrations was observed and in another set of experiments, lipid peroxidation & glutathione (GSH) depletion were induced in the presence of the tested drug candidate. Interestingly, drug candidate 1 demonstrated selective cytotoxic activity for the DU-145 cancer cell line with LC 50 value of 3.2 μM which was further visualized by confocal microscopy.

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Biological evaluation of dinuclear copper complex/dichloroacetic acid cocrystal against human breast cancer: design, synthesis, characterization, DFT studies and cytotoxicity assays

Abstract: Binuclear copper(ii) cocrystal “[Cu2(valdien)2⋯2Cl2CHCOOH],” 1 was synthesized from H2valdien scaffold and anticancer drug pharmacophore “dichloroacetic acid” embedded with two Cu(ii) connected via a hydrogen bonded network.

Cited by 39 publications

References 90 publications

Design, Synthesis, and Biological Evaluation of Benzimidazole-Derived Biocompatible Copper(II) and Zinc(II) Complexes as Anticancer Chemotherapeutics

Design, Synthesis, and Biological Evaluation of Benzimidazole-Derived Biocompatible Copper(II) and Zinc(II) Complexes as Anticancer Chemotherapeutics

Bioactive mono/bis (carboxyamide) based Co (II), Ni (II) and Cu (II) complexes: Synthesis, Characterization, DNA binding and Anticancer Potentials

Chromone‐Appended Zn(II) tRNA‐Targeted Potential Anticancer Chemotherapeutic Agent: Structural Details, in vitro ct‐DNA/tRNA Binding, Cytotoxicity Studies And Antioxidant Activity

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