In vitro cytotoxcity and interaction of new steroidal oxadiazinanones with calf thymus DNA using molecular docking, gel electrophoresis and spectroscopic techniques

Dar, Ayaz Mahmood; Ishrat, Urfi; Yaseen, Zahid; Shamsuzzaman, _; Gatoo, Manzoor Ahmad

doi:10.1016/j.jphotobiol.2015.04.031

Cited by 13 publications

(5 citation statements)

References 48 publications

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“…Thus, the topoisomerase acts as an endogeneous poison and may induce apoptosis [23]. In continuation of our previous work [24] herein, we report the synthesis of new steroidal imidazolidinones as metal free DNA binding agents. The presence of -NH or -CO groups in the molecules can cooperatively participate in the interaction with DNA via hydrogen bonding.…”

Section: Introductionsupporting

confidence: 54%

DNA Interaction Studies and In Vitro Cytotoxicity of Newly Synthesized Steroidal Imidazolidinones

et al. 2015

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New steroidal imidazolidinone derivatives (7-9) were synthesized after reacting steroidal thiosemicarbazones with oxalyl chloride in absolute ethanol. After characterization by spectral and analytical data, the interaction studies of compounds (7-9) with DNA were carried out by UV-vis, fluorescence spectroscopy, circular dichroism, molecular docking and gel electrophoresis. The compounds bind to DNA preferentially through electrostatic and hydrophobic interactions with Kb; 2.31 × 10(4) M(-1), 2.57 × 10(4) M(-1) and 2.16 × 10(4) M(-1), respectively indicating the higher binding affinity of compound 8 towards DNA. Gel electrophoresis demonstrated that the compounds 7-9 show strong interaction during the cleavage activity with pBR322 DNA. The docking study suggested the intercalation of imidazolidinone moiety of steroid derivative in minor groove of DNA. During in vitro cytotoxicity, compounds 7-9 revealed potential toxicity against the different human cancer cells (MTT assay). Apoptotic degradation of DNA in presence of compounds 7-9 was analyzed by agarose gel electrophoresis and visualized by ethidium bromide staining (comet assay). FACS analysis shows that the compound 8 bring about cell cycle arrest at 7 μM concentration.

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Section: Introductionsupporting

confidence: 54%

DNA Interaction Studies and In Vitro Cytotoxicity of Newly Synthesized Steroidal Imidazolidinones

et al. 2015

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“…For the plasmid DNA system, the migration order on the gel is as follows: Form I (SC) > Form III (L) > Form II (NC). [ 82 ] The results showed the cleavage effects upon the exposure of the plasmid to the H 2 L free ligand and its complexes in the absence (Figure 7a) and the presence (Figure 7b) of UV irradiation. The photocleavage experiment claimed that the DNA cleavage effect of the tested compounds was enhanced upon UV irradiation.…”

Section: Resultsmentioning

confidence: 99%

Design, synthesis, spectral characterization, photo‐cleavage, and in vitro evaluation of anticancer activities of new transition metal complexes of piperazine based Schiff base‐oxime ligand

Ragab

Soliman

Shehata

et al. 2022

Applied Organom Chemis

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The newly synthesized Schiff base‐oxime ligand, namely, (2Z,3E)‐3‐((3‐(4‐(3‐(((2E,3E)‐3‐(hydroxyimino)butan‐2‐ylidene)amino)propyl)piperazin‐1‐yl)propyl)imino)butan‐2‐one oxime (H2L) and its Co (II), Cu (II), and Zn (II) complexes were reported. The characterization was accomplished with the aid of CHN‐EA, mass, fourier transform infrared spectroscopy (FT‐IR), electronic spectra, magnetic moment, molar conductance and TGA. According to the spectroscopic approaches, the synthesized ligand (H2L) may act as a tetradentate or hexadentate (bis‐tridentate) coordinating ligand through the azomethine nitrogen, piperazinyl nitrogens, and oximato‐nitrogens affording distorted square planar mononuclear Co (II) complex or tetrahedrally distorted square planar binuclear Cu (II) and Zn (II) complexes whereas the coordination mode varies according to the nature of the metal ion. The microbial resistance of all the synthesized compounds was evaluated and reported. Findings showed that the Cu (II) complex has mostly the highest inhibitory effects against all tested microbial strains. Besides, the anticancer nature of the studied compounds was also evaluated against a panel of three different human cancer cells, including (HCT‐116), (MDA‐MB‐231), (HepG2) in addition to the (WI‐38) used as a healthy cells. In general, the Cu (II) complex displayed the best cytotoxic profiles against the tested cells than the Co (II) and Zn (II) complexes with negligible toxicity towards the (WI‐38) normal cells. The DNA cleavage activities of all tested compounds were assayed against pBR322 plasmid DNA. Whereas, the Cu (II) complex showed the highest DNA cleavage propensity, which proceeds predominantly via the oxidative mechanism. Additionally, flow cytometric analysis dictates that the Cu (II) complex induces cell cycle arrest in S‐phase and apoptotic cell death on HCT‐116 cells. The morphological transformations distinguished in HCT‐116 cells treated with Cu (II) complex have been depicted with the aid of scanning electron microscopy (SEM). The docking results indicate that the Cu (II) complex strongly interacts with human colon cancer (6GUE), Escherichia coli (3T88), Klebsiella pneumoniae (4HL2), and Staphylococcus aureus (3WQU) proteins, through different modes of interactions that harmonize successfully with the experimental results.

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“…The degree of DNA damage can be determined with comet assay. Some indicators, such as OTM, head optical density and tail DNA percentage, were widely used to reflect the degree of DNA damage . Therefore, comet assay of cells induced by NPS was carried out under alkaline conditions.…”

Section: Results and Discussmentioning

confidence: 99%

Molecular toxicity of nanoplastics involving in oxidative stress and desoxyribonucleic acid damage

Zheng

Yuan

Liu

2019

J of Molecular Recognition

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Microplastic pollution attracted extensive attention because of its global presence and adverse effects on ecosystem. However, it is insufficient to clear the effects of nanoplastics on organisms at the molecular level. Herein, a nanopolystyrene (50 nm) was used to examine molecular responses of superoxide dismutase (SOD) and desoxyribonucleic acid (DNA) using spectroscopy (UV-vis, circular dichroism spectra, and fluorescence measurements) and single cell gel electrophoresis methods.Results showed that nanopolystyrene induced oxidative stress, involving in the increase of SOD activity and malondialdehide (MDA) content, and DNA damage because of the significant increase of olive tail moment, head optical density, and tail DNA percentage in the groups at exposure concentrations above 5 × 10 −6 mol/L. The second structural and microenvironment of aromatic amino acids of SOD were changed with nanopolystyrene exposure. The fluorescence of SOD was quenched by nanopolystyrene at exposure concentration above 1 × 10 −5 mol/L, and the quenching mode could be ascribed to the static type. The results and the combined methods are favorable to explore the molecular toxicity of other nanoplastics and the interaction mechanism.

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In vitro cytotoxcity and interaction of new steroidal oxadiazinanones with calf thymus DNA using molecular docking, gel electrophoresis and spectroscopic techniques

Cited by 13 publications

References 48 publications

DNA Interaction Studies and In Vitro Cytotoxicity of Newly Synthesized Steroidal Imidazolidinones

DNA Interaction Studies and In Vitro Cytotoxicity of Newly Synthesized Steroidal Imidazolidinones

Design, synthesis, spectral characterization, photo‐cleavage, and in vitro evaluation of anticancer activities of new transition metal complexes of piperazine based Schiff base‐oxime ligand

Molecular toxicity of nanoplastics involving in oxidative stress and desoxyribonucleic acid damage

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