A novel palladium(II) antitumor agent: Synthesis, characterization, DFT perspective, CT-DNA and BSA interaction studies via in-vitro and in-silico approaches

Feizi-Dehnayebi, Mehran; Dehghanian, Effat; Mansouri‐Torshizi, Hassan

doi:10.1016/j.saa.2020.119215

Cited by 57 publications

(20 citation statements)

References 78 publications

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“…The flow time was measured using a digital stopwatch and each sample was tested three times to get accurate outcomes. The relative viscosity was determined using the following relation 45 where ƞ and ƞ o defines the viscosities of DNA in the presence and absence of 4g respectively, t DNA is the average flow time of pure DNA, t complex is the average flow time of DNA in the presence of 4g at varying concentration, and t o be the flow time of Tris–HCl buffer 46 . If a ligand binds via intercalary mode an increase in viscosity will be observed however, no effect on viscosity will be detected in case of groove binders 47 .…”

Section: Resultsmentioning

confidence: 99%

Visible-light driven regioselective synthesis, characterization and binding studies of 2-aroyl-3-methyl-6,7-dihydro-5H-thiazolo[3,2-a]pyrimidines with DNA and BSA using biophysical and computational techniques

Aggarwal

Jain

Sharma

et al. 2021

Sci Rep

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In recent times, fused azaheterocycles emerged as impressive therapeutic agents. Binding studies of such azaheterocycles with biomolecules is an important subject for pharmaceutical and biochemical studies aiming at the design and development of new drugs. Fused heterocyclic scaffolds, such as thiazolopyrmidines have long been used in the pharmaceutical industry for the treatment of various diseases. In this study, we have accomplished a regioselective synthesis of 2-aroyl-3-methyl-6,7-dihydro-5H-thiazolo[3,2-a]pyrimidines by the reaction of tetrahydropyrimidine-2(H)-thione with α-bromo-1,3-diketones, generated in situ from 1,3-diketones and NBS, using visible light as an inexpensive, green and renewable energy source under mild reaction conditions with wide-ranging substrate scope. The regioisomer was characterized unambiguously by 2D-NMR [1H-13C] HMBC and [1H-13C] HMQC spectroscopy. In silico toxicity data analysis showed the low toxicity risks of the synthesized compounds. Computational molecular docking studies were carried out to examine the interaction of thiazolo[3,2-a]pyrimidines with calf-thymus DNA (ct-DNA) and Bovine Serum Albumin (BSA). Moreover, different spectroscopic approaches viz. steady-state fluorescence, competitive displacement assay, UV–visible and circular dichroism (CD) along with viscosity measurements were employed to investigate the binding mechanisms of thiazolo[3,2-a]pyrimidines with DNA and BSA. The results thus obtained revealed that thiazolo[3,2-a]pyrimidines offer groove bindings with DNA and showed moderate bindings with BSA.

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Section: Resultsmentioning

confidence: 99%

Visible-light driven regioselective synthesis, characterization and binding studies of 2-aroyl-3-methyl-6,7-dihydro-5H-thiazolo[3,2-a]pyrimidines with DNA and BSA using biophysical and computational techniques

Aggarwal

Jain

Sharma

et al. 2021

Sci Rep

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“…UV-Vis spectra demonstrate four bands at 313 (log ε = 1.43), 305 (1.45), 248 (3.84) and 202 (2.92) may be assigned to intraligand π → π* and n → π* transition of CSS − group and 2,2-bipyridine ligand. Molar conductivity 123 cm 2 ohm −1 mol −1 illustrating 1:1 electrolyte [36]. Figure 1 shows the proposed reaction pathway for the above procedure followed by characterization data.…”

Section: 2'-bipyridinepyrrolinedithiocarbamatopalladium(ii) Nitrate C...mentioning

confidence: 99%

Probing the biomolecular (DNA/BSA) interaction by new Pd(II) complex via in-depth experimental and computational perspectives: synthesis, characterization, cytotoxicity, and DFT approach

2022

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Scientists should not forget that the rate of death as a result of cancer is far more than that of other diseases like influenza or coronavirus , so the research in this field is of cardinal significance. Therefore, a new and hydrophilic palladium(II) complex of the general formula [Pd(bpy)(proli-dtc)]NO 3 , in which bpy and proli-dtc are 2,2'-bipyridine and pyrroline dithiocarbamate ligands, respectively, was synthesized and characterized utilizing spectral and analytical procedures. Density functional theory (DFT) calculation was also performed with B3LYP method in the gas phase. The DFT and spectral analysis specified that the Pd(II) atom is found in a square-planar geometry. HOMO/LUMO analysis, quantum chemical parameters and MEP surface of the complex were investigated to acquire an intuition about the nature of the compound. Partition coefficient and water solubility determination showed that both lipophilicity and hydrophilicity of the compound are more than cisplatin. The 50% inhibition concentration (IC 50 ) value was evaluated against K562 cancer cells, the obtained result has revealed a promising cytotoxic effect. DNA and BSA binding of the complex were explored through multi-spectroscopic (UV-Vis, fluorescence, FRET, and CD) and non-spectroscopic (gel electrophoresis, viscosity and docking simulation) techniques. The obtained findings demonstrated that the complex strongly interacts with CT-DNA by hydrophobic interactions and possesses medium interaction with BSA via hydrogen bond and van der Waals forces, thus BSA could efficiently carry out complex transportation. Furthermore, the results of docking simulation agree well with the experimental findings. In conclusion, the new Pd(II) complex has cytotoxic activity and could interact with DNA and BSA effectively.

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“…The Tris-HCl buffer was prepared using deionized, triple distilled water. The solution of CT-DNA in the buffer gave a 2 -1 ratio of UV-Visible absorption at 260 and 280 nm, [18], meaning that the DNA was sufficiently free of protein. The concentration of DNA was measured by spectrophotometry (ε = 6,600 mol.dm -3 .cm -1 ) [26].…”

Section: Materials and Reagentsmentioning

confidence: 99%

“…In general, it was reported that the positive shift (anodic shift) in formal potential is caused by the intercalation of the cationic drug into the double helical structure of DNA, while negative shift is observed for the electrostatic interaction of the cationic drug with the anionic phosphate of DNA backbone [50,51]. The obvious negative peak potential shift (cathodic shift) in the CV behavior of complex (1) by the addition of DNA suggests an electrostatic interaction of complex (1) with the [18], but with much stronger binding affinity, due to hydrogen bonding of glycine to the electronegative sites of DNA. Wherase, the positive shift in formal potential of complex (2) (i.e from E1/2 (-685 mV) to E1/2 (-628 mV)) supports our previous inference for intercalation binding mode of complex (2), where the cyclobutane ring undergo stacking interaction with the sugar group of the bound DNA as previously proposed and form hydrophobic contact with the purine rings of IMP and GMP.…”

Section: Cyclic Voltammetry Measurementsmentioning

confidence: 99%

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Synthesis, Speciation, DNA Binding, Electrochemical and Antiproliferative Properties of Pd(II) Complexes Designed to Improve the Interaction with DNA

2021

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With the success of cisplatin, further extensive research activities resulted in the discovery of carboplatin (a second-generation drug), where the chloride is replaced by 1,1-cyclobutanedicarboxylate as a new leaving group. In the current study, we continue our previous work on the binding behavior of [Pd(byp)(H2O)2] 2+ with structural features that enhance the interaction with DNA. The coordination properties of 2,2´-bipyridine ligand have been changed such that a versatile ligand can be formed. [Pd(byp)(gly)] + (1) and [Pd(byp)(CBDCA)] (2), where byp is 2,2´-bipyridine, gly is glycine, and CBDCA is cyclobutane-1,1´-dicarboxylic acid, were synthesized and characterized. The stability constants and stoichiometries of the complexes formed between various DNA unit constituents and [Pd(byp)(H2O)2] 2+ were investigated. The binding properties of the complexes ( 1) and ( 2) with CT-DNA were analyzed by UV-vis spectroscopy, viscosity measurements, and cyclic voltammmetry. The determined binding constants for both complexes show strong binding to CT-DNA. The (Kb) values of both complexes are found to be greater than that reported in our previous finding for [Pd(byp)(H2O)2] 2+ . The determined (Kb) value for complex (1) (Kb= 4.36x10 3 M −1 ) as a cationic intercalator, suggests an electrostatic binding mode of the positively charged complex (1) together with hydrogen bonding with the negative sites of the bound DNA. The comparatively higher (Kb) value measured for complex (2) (Kb= 2.11x10 4 M −1 ) indicates an intercalation mode of binding whereby a ring-opening reaction of CBDCA occurs, followed by the reaction with guanosine 5'-monophosphate to form [(Pdbyp)(CBDCA-O)(5'-GMP)]. The small change in the measured ΔTm following binding of complex (1) supports strong electrostatic binding, while the significant change in ΔTm obtained for complex (2) supports the intercalation mode of binding. The two complexes in the absence and in the presence of CT-DNA show quasi-reversible oxidation-reduction redox CV wave . The variation in the values of E1/2, Ep and Ipc/Ipa also supports the electrostatic binding of the complex (1) and the intercalation mode for complex (2). The antitumor effects of the two complexes were tested against two different types of cancer cell lines, breast cancer (MCF-7) and colon cancer (HCT-116), as well as one normal cell line; the human normal melanocytes (HFB4). The two complexes display dose-dependent anti-proliferation activity. Complex (2) was shown to have more efficient apoptosis than Complex (1) and may be considered a model for carboplatin with a prediction of improved efficacy against cancer.

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A novel palladium(II) antitumor agent: Synthesis, characterization, DFT perspective, CT-DNA and BSA interaction studies via in-vitro and in-silico approaches

Cited by 57 publications

References 78 publications

Visible-light driven regioselective synthesis, characterization and binding studies of 2-aroyl-3-methyl-6,7-dihydro-5H-thiazolo[3,2-a]pyrimidines with DNA and BSA using biophysical and computational techniques

Visible-light driven regioselective synthesis, characterization and binding studies of 2-aroyl-3-methyl-6,7-dihydro-5H-thiazolo[3,2-a]pyrimidines with DNA and BSA using biophysical and computational techniques

Probing the biomolecular (DNA/BSA) interaction by new Pd(II) complex via in-depth experimental and computational perspectives: synthesis, characterization, cytotoxicity, and DFT approach

Synthesis, Speciation, DNA Binding, Electrochemical and Antiproliferative Properties of Pd(II) Complexes Designed to Improve the Interaction with DNA

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