Intercalative Binding Mode Research Articles

Synthesis, Characterization, Biological Activity and Molecular Docking Studies of Novel Organotin(IV) Carboxylates.

Four new carboxylates complexes with general formula R2SnL2 and R3SnL, where R = n-butyl (1, 3), methyl (2, 4) and L = 4-Chlorophenoxyacetate, were synthesized in significant yields. FT-IR analysis revealed a chelating (1 and 2) and a bridging bidentate (3 and 4) coordination modes for the carboxylate ligand in solid state which was further confirmed by the single crystal X-ray analysis of complex 4. The NMR data (1H, 13C and 119Sn) revealed a higher coordination number around the tin center in R2SnL2 (1 and 2) compared to R3SnL (3 and 4). A close matching was observed between the experimental and calculated structures (obtained at B3LYP/6-31G* + LANL2DZ basis set). Quantum chemical analysis indicates that the carboxylate moiety has the major contribution in the formation of filled and unfilled orbitals as well as in ligand to ligand intramolecular charge transfer during the electronic transitions. The cytotoxicity data of the screened compounds evaluated against lung cancer cell line (A549) and normal lung fibroblast cell line (MRC-5) revealed that 1, 3 and 4 have shown dose dependent cytotoxic effects while HL and 2 have shown steady and low cytotoxic activities. The antibacterial activity of complexes 1–4 is higher than that of HL. Molecular docking study showed an intercalation binding mode for complex 3 with DNA (docking score = −3.6005) involving four polar interactions. Complex 3 docking with tubulin (PDB ID 1SA0) with colchicine as a target protein resulted in three polar interactions (docking score −5.2957). Further, the docking analysis of the HL and 1–4 has shown an adequate interactions with the coronavirus SARS-CoV-2 spike protein, nucleocapsid protein and human angiotensin converting enzyme (ACE2).

Multifunctional carbon dot anchored halloysite nanotube: Nanovehicle for cisplatin drug release, cytotoxicity on breast cancer cells and DNA binding studies

Halloysite nanotube (HNT) is a clay material paving much attention in the field of biological studies. In the present work multifunctional carbon dot (CD) has been synthesized and functionalized with HNT that resulted in HNT-CD nanocomposite. Fabricated HNT-CD nanocomposite has been subjected to analytical and morphological characterization using XRD, FTIR, SEM and EDX techniques and indicates proper functionalization of CD with HNT. Cisplatin has been evaluated for drug loading efficiency for HNT and HNT-CD nanocomposite and found encapsulation efficiency and loading capacity is high for the nanocomposite. Cisplatin release studies with HNT and HNT-CD have been conducted at different pH. Cisplatin loaded with HNT and HNT- CD was further evaluated for in-vitro cytotoxicity test against MCF-7 cells. Cisplatin-loaded HNT- CD nanocomposite showed greater toxicity against MCF-7 cell lines compared to HNT alone. HNT-CD nanocomposite was further evaluated for its capacity to interact with Ct-DNA using UV–visible, Fluorescence spectrophotometry and circular dichroism using spectropolarimeter. The ∆G value for the HNT-CD was found to be 27.91 KJ mol −1 indicates a spontaneous binding process with Ct-DNA. The obtained n value close to 1, suggests the existence of a single binding site between the HNT-CD hybrid and Ct-DNA. The circular dichroism results are in good agreement with findings of the absorption and emission studies and indicate association with intercalative binding mode of HNT-CD hybrid with Ct-DNA.

Idarubicin/mithramycin-acridine orange combination drugs co-loaded by DNA nanostructures: Different effects of intercalation and groove binding on drug release and cytotoxicity

The co-loading of chemotherapy-phototherapy (CTPT) combination drugs by aptamer-targeted DNA nanostructures has significant advantages in improving anticancer effects and overcoming the multidrug resistance of cancer cells. The different binding modes of drugs to DNA nanostructures may impact CTPT therapy. Here, the anti-drug resistance effects of idarubicin (IDA) or acridine orange (AO) as single drug, as well as IDA/mithramycin (MTR) dimers ((MTR)2Zn2+) + AO combination drugs loaded by AS1411-tethered DNA nanotrains (AS1411NTrs), were studied. The intercalative binding mode between IDA/AO and AS1411NTrs was verified through measurements of viscosity, changes in melting temperature, and potassium iodide quenching. A series of thermodynamic parameters such as the binding constant and the number of binding sites were obtained through fluorescence spectroscopy, isothermal titration calorimetry, and differential scanning calorimetry. The high binding constants and the number of binding sites indicated that AS1411NTrs had a high loading capacity for IDA and AO. An in vitro release study showed that the release rate and release model of IDA/(MTR)2Zn2+/AO in the binary and ternary systems with or without deoxyribonuclease I were related to their binding mode and order of addition. An in vitro cytotoxicity study proved that the cytotoxicity and synergistic effects of the three drugs to human breast cancer MCF-7 cells and multidrug-resistant MCF-7/ADR cells were enhanced due to loading of AS1411NTrs. The IDA/(MTR)2Zn2+ + AO combination drugs could more obviously enhance apoptosis of MCF-7/ADR cells as confirmed by cell apoptosis assays. The cell uptake study demonstrated that IDA/(MTR)2Zn2+/AO loaded by AS1411NTrs was mainly concentrated in the nucleus of MCF-7/ADR cells. This work will provide theoretical information for combination therapy of IDA/(MTR)2Zn2+ and AO based on DNA nanostructures.

Lanthanide (III) complexes (Ln = Er and Yb) based on polypyridyl ligand: Synthesis, crystal structure, DNA-binding activity and interaction with human serum protein in vitro

Two lanthanide complexes [Er(acac)2(o-NPIP)2](CH3CH2OH)2 (1) and [Yb(acac)2(o-NPIP)2](NO3)2 (2) (acac = acetylacetonate, o-NPIP = 2-(2-nitrophenyl)imidazo[4,5-f]1,10-phenanthroline) have been synthesized and characterized by X-ray single-crystal analysis, IR and electronic spectra. The two complexes are isostructural, which crystallizes in the triclinic crystal system. By binding two types of o-NPIP ligands and acetylacetonate molecules, Ln(III) (Ln = Er and Yb) ion shows a distorted square antiprism geometry. That DNA binding and human serum albumin (HSA) interacting with Ln (III) complexes have been investigated by UV–Vis spectra, fluorescent spectra and agarose gel electrophoresis. Both complexes showed moderate intercalative binding mode and oxidative cleavage ability with DNA. In addition, complexes 1 and 2 quenched the intrinsic fluorescence of HSA effectively by static mechanism. The binding molecular number was about one between two complexes and HSA. Moreover, the thermodynamic parameters ΔG, ΔH and ΔS revealed that two complexes combined with HSA through hydrophobic interactions.

Copper(II) complexes as novel anticancer drug: Synthesis, spectral studies, crystal structures, in silico molecular docking and cytotoxicity

Three novel mixed ligand complexes of copper, derived from the parent cyclohexylthiosemicarbazones were synthesized along with the secondary ligands such as 2-picoline and 5,5’-dimethylbipyridine. They are characterised by elemental analysis, spectroscopic techniques (IR, UV-vis) and X-ray crystallography. The single crystal X-ray structure showed that the complex 1 is having distorted square pyramidal geometry and complex 2 is having distorted square planar geometry. The complex 3 is a 1D polymer. The interaction of complexes with CT-DNA was studied by absorption spectral titration and fluorescent measurements. The observed data shows that the complexes bind with CT-DNA via an intercalative mode of binding. Efficient PTZ57R (bp: 2886) cleavage ability of the synthesized compounds were explored by gel electrophoresis. Molecular docking studies of the Cu(II) complexes with corresponding DNA protein were carried out. An in vitro cytotoxicity study of the complex was carried out against MDA-MB-231 breast cancer cell line.

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

AbstractA 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 LC50 value of 3.2 μM which was further visualized by confocal microscopy.

2-Amino-5-substituted-1,3,4-oxadiazole as chemosensor for Ni(II) ion detection: antifungal, antioxidant, DNA binding, and molecular docking studies.

An oxadiazole derivative 2 was prepared by condensation reaction through cyclization of semicarbazone in the presence of bromine; the structural confirmation was supported by 1 H and 13 C nuclear magnetic resonance (NMR) spectroscopy, Fourier transform-infrared spectroscopy, and liquid chromatography-mass spectrometry. Its sensing ability towards Ni2+ ion was examined showing a binding constant of 1.04 × 105 compared with other suitable metal cations (Ca2+ , Co2+ , Cr3+ , Ag+ , Pb2+ , Fe3+ , Mg2+ , and K+ ) using ultraviolet-visible (UV-vis) and fluorescence spectroscopic studies. The minimum concentration of Ni2+ ions and limit of detection was found to be 9.4 μM. A job's plot gave the binding stoichiometry ratio of oxadiazole derivative 2 vs Ni2+ ions as 2:1. Furthermore, the intercalative binding mode of oxadiazole derivative 2 with calf thymus DNA was supported by ultraviolet-visible (UV-vis) and fluorescent light, viscosity, cyclic voltammetry, time-resolved fluorescence, and circular dichroism measurements. The molecular docking result gave the binding score for oxadiazole derivative 2 as -6.5 kcal/mol, which further confirmed the intercalative interaction. In addition, the antifungal activity of oxadiazole derivative 2 was also screened against several fungal strains (C. albicans, C. glabrata, and C. tropicalis) by broth dilution and disc diffusion methods. In antioxidant studies, the oxadiazole derivative 2 showed potential scavenging activity against 2,2-diphenyl-1-picrylhydrazyl and H2 O2 free radicals.

Green synthesized silver nanoparticles obtained from Stachys schtschegleevii extract: ct-DNA interaction and in silico and in vitro investigation of antimicrobial activity

The aim of this study was the synthesis of Ag nanoparticles (AgNPs) by using Stachys schtschegleevii extract and checking the composition, morphology and size of the green synthesized AgNPs using the analytical techniques (UV–vis, DLS, zeta potential, SEM-EDX, FT-IR and TEM). The TEM images of AgNPs represent a smooth surface and are spherical in shape with an average particle size of 31.43 nm. The antioxidant activities of green synthesized AgNPs were appraised by radical scavenging 1, 1-diphenyl-2-picrylhydrazyl test and the green synthesized AgNPs showed a strong ability to scavenge free radicals. In addition, AgNPs displayed a remarkable antibacterial and antifungal activity against various microorganisms. We employed molecular docking to investigate the AgNPs interaction with Dihydrofolate reductase (DHFR) of Escherichia coli, Staphylococcus aureus, and Candida albicans and there is a good agreement between molecular docking and our experimental results. The result of ct-DNA–AgNPs interaction demonstrated that AgNPs can bind to ct-DNA through partial intercalation binding mode. Communicated by Ramaswamy H. Sarma

Molecular engineering of complexation between RNA and biodegradable cationic gemini surfactants: role of the hydrophobic chain length

The effects of the hydrophobic alkyl chain length of Cm-E2O-Cm gemini surfactants (m = 12, 14 and 16) on ribonucleic acid were investigated using different methods. The various calculated parameters revealed that complexation occurs via an intercalative binding mode.

Comprehensive biological {DNA/RNA binding profile, cleavage &cytotoxicity activity} of structurally well-characterized chromone-appended Cu(II)(L1-3)(phen) potential anticancer drug candidates

A series of chromone-appended copper(II)(phen) complexes (1–3) having the general formulae [Cu(L1)(phen)(H2O)2(NO3)] 1, [Cu(L2)(phen)(NO3)] 2 and [Cu(L3)(phen)(NO3)] 3, where L1 = 3-formylchromone, L2 = 6-fluoro-3-formylchromone, L3 = 6-bromo-3-formylchromone and phen = 1,10-phenanthroline were prepared to examine the effect of halogen on structure activity relationship. The molecular solid state structure of (1–3) was fully characterized by employing various spectroscopic techiques, single crystal X-ray diffraction studies and DFT B3LYP (gas phase) computations. Comparative in vitro binding studies of (1–3) with ct-DNA and tRNA were conducted by using a battery of optical {UV–vis, fluorecence and circular dichoric} and electrochemical methods, which implicated strong binding through non-covalent π-π stacking intercalative binding mode. The order of binding was found to be 3 ˃ 2 ˃1 as determined by Kb and Ksv values with bromo analog 3 exhibiting the strongest binding affinity for both ct-DNA and tRNA nucleobases, however, underlining more avid predisposed binding with tRNA as compared to ct-DNA. The cleavage activity of (1–3) was studied by electrophoretic assay using pBR322 DNA and tRNA, which exhibited efficient DNA cleaving ability at low micro molar concentrations. The cleavage process was mediated by an oxidative pathway involving ROS species viz., singlet oxygen (1O2) and superoxide anions(O2•−), with more pronounced cleaving ability of bromo analog 3 as compared to unsubstituted 1 and fluoro 2 analog derivatives. Furthermore, time & concentration dependence of tRNA cleavage was also observed. The cytotoxicity activity of tested drug candidates 2 and 3 were evaluated on a panel of human cancer cell lines, viz., MCF-7, MDA-MB-231, AW13516, SiHa and Hop-62 using SRB assay which validated bromo analog 3 and 2 as good anticancer agents, broadly against all the tested cancerous strains (with GI50 values < 10) except with AW13516, SiHa and Hop-62 (GI50 values were found in the range18.00–36.8).

Macrocyclic "tet a"-Derived Cobalt(III) Complex with a N,N'-Disubstituted Hexadentate Ligand: Crystal Structure, Photonuclease Activity, and as a Photosensitizer.

A cobalt(III) complex, [Co(L)]Cl (complex 1, where L = 1,8-[N,N-bis{(3-formyl-2-hydroxy-5-methyl)benzyl}]-1,4,8,11-tetraaza-5,5,7,12,12,14-hexamethylcyclotetradecane) with distorted octahedral geometry has been synthesized and characterized using various spectroscopic techniques. The structure of the ligand has remarkably rich hydrogen intermolecular interactions such as H···H, H···C/C···H, and H···O/O···H that vary with the presence of the metal ion, and the structure of complex 1 has Cl···H interactions; this result has been proved by Hirshfeld surface and two-dimensional (2D) fingerprint maps analyses. The complex exhibits a quasi-reversible Co(III)/Co(II) redox couple with E1/2 = −0.76 V. Calf thymus DNA (CT DNA) binding abilities of the ligand and complex 1 were confirmed by spectroscopic and electrochemical analyses. According to absorption studies, the ligand and complex 1 bind to CT DNA via intercalative binding mode, with intrinsic binding strengths of 1.41 × 103 and 8.64 × 103 M–1, respectively. A gel electrophoresis assay shows that complex 1 promotes the pUC19 DNA cleavage under dark and light irradiation conditions. Complex 1 has superior antimicrobial activity than the ligand. The cytotoxicity of complex 1 was tested against MDA-MB-231 breast cancer cells with values of IC50 of 1.369 μg mL–1 in the dark and 0.9034 μg mL–1 after light irradiation. Besides, cell morphological studies confirmed the morphological changes with AO/EB dual staining, reactive oxygen species (ROS) staining, mitochondria staining, and Hoechst staining on MDA-MB-231 cancer cells by fluorescence microscopy. Complex 1 was found to be a potent antiproliferative agent against MDA-MB-231 cells, and it can induce mitochondrial-mediated and caspase-dependent apoptosis with activation of downregulated caspases. The biotoxicity assay of complex 1 on the development of Artemia nauplii was evaluated at an IC50 value of 200 μg mL–1 and with excellent biocompatibility.

Exploring the binding mode of ester-based cationic gemini surfactants with calf thymus DNA: A detailed physicochemical, spectroscopic and theoretical study

Gene therapy is a transfectant method for the treatment of hereditary disease, which transfers the gene mutation into the cells. In the view of the high prospects of utilization of cationic gemini surfactants as a non-viral vector for the gene transfection, we have made a comprehensive study on the interactions between a recently synthesized series of ester-functionalized cationic Cm-E2O-Cm gemini surfactants (m = 12, 14 and 16) with calf thymus deoxyribonucleic acid (ctDNA) utilizing various techniques. The micellization behavior of gemini surfactants has been altered in the presence of ctDNA. A series of measurements (fluorescence, UV–vis and time-resolved fluorescence) show that the quenching of ctDNA proceeds by a static mechanism. The competitive displacement studies (EB, AO and HO), KI quenching analysis, CD studies and viscosity measurements suggested intercalative binding mode in a stoichiometry ratio of 1:1 with the Kb (binding constant) order being: C16-E2O-C16 > C14-E2O-C14 > C12-E2O-C12. The thermodynamic parameters show that the geminis interacted with ctDNA spontaneously through ionic/electrostatic interactions. Furthermore, the theoretical approaches offer accurate insights about the binding of gemini surfactants with DNA, and are in consistence with the experimental results.

Spectroanalytical, computational, DNA/BSA binding and in vitro cytotoxic activity studies of new transition metal complexes of novel aryl hydrazone

The ligand ((1-ethyl-Nʹ-furan-2-yl)-methylene)-1,4-dihydro-7-methyl-4-oxo-1,8- napthyridine-3-carbohydrazide (NFMHMONC) and its transition metal (II) complexes were synthesized and characterized by various spectroanalytical techniques. The quantum chemical calculations and physicochemical properties of NFMHMONC were evaluated by HyperChem 7.5 software tools. The binding ability of metal complexes with CT-DNA has been determined by electronic absorption spectral titrations and competitive DNA binding fluorescence measurements showed a relatively high binding constant value in [Cu(II)(NFMHMONC)2]Cl2 compared to [Co(II)(NFMHMONC)2H2O]Cl2. The DNA binding behaviors were investigated by the study of viscosity measurement and the results indicated the intercalative mode of binding. The binding efficiency of metal complexes with BSA was also determined by electron absorption spectroscopy. Hydrolytic cleavage activity against supercoiled pBR322 plasmid DNA of NFMHMONC and its metal (II) complexes carried out and inferred more efficient double-strand DNA cleavage with [Cu(II)(NFMHMONC)2]Cl2 complex. The radical scavenging activity study of NFMHMONC and its metal complexes evaluated by their interaction with the DPPH free radical on electronic absorption spectroscopy has shown remarkable antioxidant activity. In vitro cytotoxicity studies revealed a lower percentage of cell viability and IC50 value in both HeLa and MCF-7 cell lines with [Cu(II)(NFMHMONC)2]Cl2 compared to [Co(II)(NFMHMONC)2H2O]Cl2 and NFMHMONC.

Tris-(2-pyridyl)-pyrazolyl Borate Zinc(II) Complexes: Synthesis, DNA/Protein Binding and In Vitro Cytotoxicity Studies.

Zn(II) complexes bearing tris[3-(2-pyridyl)-pyrazolyl] borate (Tppy) ligand (1–3) was synthesized and examined by spectroscopic and analytical tools. Mononuclear [TppyZnCl] (1) has a Zn(II) centre with one arm (pyrazolyl-pyridyl) dangling outside the coordination sphere which is a novel finding in TppyZn(II) chemistry. In complex [TppyZn(H2O)][BF4] (2) hydrogen bonding interaction of aqua moiety stabilizes the dangling arm. In addition, solution state behaviour of complex 1 confirms the tridentate binding mode and reactivity studies show the exogenous axial substituents used to form the [TppyZnN3] (3). The complexes (1–3) were tested for their ability to bind with Calf thymus (CT) DNA and Bovine serum albumin (BSA) wherein they revealed to exhibit good binding constant values with both the biomolecules in the order of 104–105 M−1. The intercalative binding mode with CT DNA was confirmed from the UV-Visible absorption, viscosity, and ethidium bromide (EB) DNA displacement studies. Further, the complexes were tested for in vitro cytotoxic ability on four triple-negative breast cancer (TNBC) cell lines (MDA-MB-231, MDA-MB-468, HCC1937, and Hs 578T). All three complexes (1–3) exhibited good IC50 values (6.81 to 16.87 μM for 24 h as seen from the MTS assay) results which indicated that these complexes were found to be potential anticancer agents against the TNBC cells.

Interaction of an electrochemical redox indicator new methylene blue with DNA using biophysical techniques

Electrochemical biosensors (an integrated system of biological constituent and physiochemical detector) have attracted plenty of attention due to its high precision, and importance in clinical diagnosis. In electrochemical biosensors, redox indicators like methylene (MB) blue are used to detect the electrical changes, which by intercalating between DNA base pairs, can produce an intense redox signal on the surface of ssDNA modified electrode. This study reports the interaction between calf thymus DNA (ctDNA) and new methylene blue (NMB), having almost identical basic skeleton to MB. Various techniques like UV-Visible, thermal melting, fluorescence, circular dichroism (CD) spectroscopy and molecular docking have been utilized. Hypochromism and a red shift in UV-Vis spectra revealed the intercalation binding mode for DNA-NMB complex. Nearly identical binding constants were calculated using UV-Visible and fluorescence spectroscopy. The calculated thermodynamic parameters like change in enthalpy (ΔH°) and entropy (ΔS°) were found to be -6.11×104 and -128.96 JK-1mol-1 at 290 K respectively. CD revealed a change into more compact B-DNA conformation after binding with NMB. These studies suggest that intercalation mode, hydrogen bonding, and van der Waals forces might be responsible for DNA-NMB interaction. This work might further facilitate our understanding about DNA-drug interactions for utilizing them for medicinal purposes and nanochemistry.

Glutamine conjugated organotin(IV) Schiff base compounds: Synthesis, structure, and anticancer properties

AbstractHerein, glutamine conjugated organotin(IV) Schiff base compounds, [(SBGlu‐Naph)Sn (Me)2] (1), [(SBGlu‐Naph)Sn(n‐Bu)2] (2), [(SBGlu‐Sali)Sn (Me)2] (3), [(SBGlu‐Sali)Sn(n‐Bu)2] (4) and [(SBGlu‐Sali)Sn (Ph)2] (5), were synthesized by one‐pot reaction with an aldehyde (2‐hydroxy‐1‐naphthaldehyde) for 1 and 2, and 5‐methyl‐2‐hydroxybenzaldehyde (for 3–5) and respective diorganotin oxide. The compounds were characterized using elemental micro‐analyses, spectroscopic techniques (FT‐IR, 1H NMR, 13C NMR, and 119Sn NMR), mass spectrometry, and single‐crystal X‐ray diffraction analyses. Based on in‐silico ADME (absorption, distribution, metabolism, and excretion) and drug‐likeness properties, compounds 1, 3, and 4 were selected to investigate their DNA/Protein binding properties with calf thymus DNA (CT‐DNA) and bovine serum albumin (BSA) using spectrophotometry and spectrofluorimetry. The intercalative mode of binding with CT‐DNA was supported by molecular docking simulations. The emission spectral data of compounds with CT‐DNA showed 1 as a groove binder, and 3 and 4 as an intercalator which was confirmed by competitive displacement assays. Similarly, static and dynamic mode of interaction between the compounds and BSA was found. Furthermore, these compounds were screened for their cytotoxic activity against two human cancer cell lines; PC‐3 (Prostate) and Mg‐63 (Osteosarcoma) at different concentrations. Quantitative structure–activity relationship (QSAR)‐based regression models were developed and implemented on compounds 1, 3, and 4 that inferred compound 3 to be the most potential candidate for further in vivo studies.

A green and sensitive guanine-based DNA biosensor for idarubicin anticancer monitoring in biological samples: A simple and fast strategy for control of health quality in chemotherapy procedure confirmed by docking investigation

Drug efficiency can be considerably boosted while adverse effects can be reduced by precisely monitoring the concentration of anti-cancer drugs. Thus, one of the most important parameters for human health is the monitoring and detection of anticancer drugs during chemotherapy treatment. Herein, a glassy carbon electrode (GCE) was modified by Pt- and Pd-incorporated ZnO nanoparticles-decorated single-wall carbon nanotubes (Pt–Pd–ZnO/SWCNTs) nanocomposites, and ds-DNA (Calf Thymus) that was a biological recognition element, and it was aimed to be utilized as an ultrasensitive and effective electroanalytical biosensor for idarubicin (IDR) monitoring. Various physicochemical characterization techniques including transmission electron microscopy (TEM), field-emission scanning electron microscopy (FE-SEM) with energy-dispersive X-ray spectroscopy (EDS) were used to investigate the morphology and structure of the Pt–Pd–ZnO/SWCNTs nanocomposite, which was produced via straightforward chemical precipitation combined with the one-pot method. The layer-by-layer modification technique was implemented to fabricate the ds-DNA/Pt–Pd–ZnO/SWCNTs/GCE to be further utilized as a voltammetric sensor for sensitive monitoring of idarubicin in biological fluids and pharmaceutical substances. The electroanalytical method implemented to detect idarubicin was based to detect the ds-DNA's guanine base signal on the surface of the modified electrode in the absence and presence of the anticancer drug. The results explicated that the developed biosensor performed well in determining idarubicin in concentrations ranging from 1.0 nM to 65 μM, with a detection limit of 0.8 nM. The idarubicin detection ability of the modified electrode in real samples was evaluated, and the recovery data was acquired in the range of 98.0% and 104.75%. In the final step, the preferential intercalative binding mode of idarubicin drug with ds-DNA was approved by molecular docking study. This study paves the way for engineering highly sensitive DNA biosensors to be employed in the monitoring of anticancer drugs by combining the benefits of nanocomposites and valuable information of a molecular docking study.

Synthesize and multi-spectroscopic studies of zinc-naproxen nanodrug as DNA intercalator agent

The zinc-naproxen complex as a nano-drug (NanoD) was synthesized successfully via effective ultrasound-assisted processes. The chemicophysical properties of the NanoD were determined using FT-IR, XRD, SEM, DLS, and EDX mapping analyses. The results confirmed the formation of the 55 nm NanoD laminates. The interaction of the obtained NanoD with calf thymus deoxyribonucleic acid (CT-DNA) was studied as well. Structural and topography changes of DNA in interaction with the NanoD were investigated by atomic force microscopy (AFM). The results of electronic absorption spectroscopy, the DNA-viscosity studies, and competition fluorescence spectroscopy showed that CT-DNA binds to the NanoD through the intercalative binding mode. The data of AFM analysis indicated swollen CT-DNA upon interaction with the NanoD. The in vitro investigation of cytotoxicity of the NanoD on HT-29, Hep G2, and B16–F10 cancer cells as well as normal HFF-1 cells. The obtained results demonstrated high cytotoxicity activity of the NanoD than that of cisplatin in the HT-29 cell line, especially at lower concentrations. On the B16–F10 cell line at lower concentrations (up to 8 μg mL−1), it is comparable to cisplatin and on the Hep G2 cell line and normal HFF-1 cell line at all concentrations, cytotoxicity of cisplatin is more than NanoD.

Structure elucidation, in vitro binding studies and ROS-dependent anti-cancer activity of Cu(II) and Zn(II) phthaloylglycinate(phen) complexes against MDA-MB-231 cells.

New mononuclear Cu(II) and Zn(II)-based complexes 1 [Cu(L)2(diimine)HOCH3] and 2 [Zn(L)2(diimine)] have been synthesized as anti-cancer chemotherapeutics targeted to tRNA. The structure elucidation of complexes 1 and 2 was carried out by spectroscopic and single X-ray diffraction studies. In vitro interaction studies of complexes 1 and 2 with ct-DNA/tRNA were performed by employing various biophysical techniques to evaluate and predict their interaction behavior and preferential selectivity at biomolecular therapeutic targets. The corroborative results of the interaction studies demonstrated that complexes 1 and 2 exhibited avid binding propensity via intercalative mode of binding toward ct-DNA/tRNA. Electrophoretic assay revealed that the complexes 1 and 2 were able to promote single- and double-strand cleavage of the plasmid DNA at low micromolar concentrations under physiological conditions in the absence of an additional oxidizing or reducing agent. RNA hydrolysis studies revealed that the complexes 1 and 2 could promote tRNA cleavage in a concentration and time-dependent manner. The cytotoxic potential of complexes 1 and 2 was evaluated against the MDA-MB-231 cell line, which showed that the complexes were able to inhibit the cell growth in a dose-dependent manner. The intracellular ROS production and mitochondrial superoxide anion assay revealed that the complexes 1 and 2 induce a dose-dependent activity, suggesting the involvement of ROS-mediated mitochondrial apoptotic pathway leading to cell death.

Cu(II) complexes of a bio-compatible aminoguanidine Schiff base: Histidine sensing and DNA-binding studies

Two Cu(II) complexes of pyridoxal-aminoguanidine Schiff base ligand with formula [Cu(HL)Cl]2(OAc)2·4H2O (1) and [Cu(HL)Cl(NCS)].H2O (2) are reported. The ligand and the complexes were characterized by their elemental analyses, ESI-MS, Uv–Vis, IR spectroscopy and cyclic voltammetric measurements. Single crystal structures of complex 1 and 2 were solved by X-ray diffraction. In both the Cu(II) complexes Cu(II) ions are in a square pyramidal geometry having geometry index (τ) value of 0.11 for complex 1 and 0.15 for complex 2. Both the complexes bind to calf-thymus DNA with binding constant comparable to ethidium bromide. Circular dichroism studies revealed an intercalative mode of binding for both the complexes. In addition, the complexes also show promising cleavage of pUC19 supercoiled plasmid DNA with 1 showing the highest cleavage activity of ∼ 99%. In addition, both the complexes selectively recognize l-histidine amino acid. The low detection limit values (0.085 μM and 0.19 μM for complexes 1 and 2, respectively) ascertain the making of an efficient l-histidine biosensor. The absorption, emission and mass spectral results establish the formation of Cu(His)2 complex, with liberation of the fluorescent free ligand as the mechanism of sensing.