Herring Sperm DNA Research Articles

New Mononuclear Metal Complexes Based on 3‐Acetyl‐4‐Hydroxy Coumarin as Potential Antitumor Agents: Full Structural Elucidation, Theoretical Calculations, and Biological Activity Studies

ABSTRACTNew transition metal complexes (M‐AHyC) have been prepared: M = Ni2+, Co2+, and Zn2+ metal ions; AHyC = 3‐acetyl‐4‐hydroxy coumarin. The synthesized complexes (M‐AHyC) were also subjected to elemental and TGA analysis, magnetic moment, and molar conductivity measurements with comprehensive spectral characterization (Fourier transform‐IR, UV‐visible, NMR, and XR diffraction). Ni2+, Co2+, and Zn2+ metal ions react with AHyC to form complexes with a stoichiometric ratio 1:2 (M:L). The results of spectral data revealed that the AHyC coordinated the central metal ions in a monoanionic bidentate manner via the carbonyl oxygen and phenolic oxygen atoms forming octahedral geometry. Against HepG‐2 cell lines, the cytotoxic properties of fabricated M‐AHyC compounds were assessed. The cytotoxic study revealed that the Zn‐AHyC complex showed significant activity to inhibit the growth of the HepG‐2 cell line. Additionally, the binding properties of M‐AHyC complexes with herring sperm DNA (HS‐DNA) have been identified using UV‐visible spectroscopy. The interaction between M‐AHyC complexes and DNA revealed a moderately strong interaction depending on the intercalative binding mode. The interaction of M‐AHyC complexes with DNA was further investigated with molecular docking simulation, which supports previously spectroscopic findings. A study on DNA cleavage using agarose gel electrophoresis has also been performed. The DFT calculations were utilized to compute chemical quantum parameters, validate the proposed structures, and provide evidence for the biological findings.

Biological Appraisals of Cisplatin and Intercalating Analogies of Nanoscale Level Metal(II) Complexes

A series of nanoscale-level metal complexes with bidentate (N2MCl[Formula: see text] and tetradentate (MN) chromophores have been employed as efficient cisplatin analogues and intercalating agents towards DNA and studied their anticancer activities against A549 cancer cells. Among them, complexes 1–6 exist with two labile chlorides similar to the chemotherapeutic inorganic drug cisplatin, which have been found to bind covalently with herring sperm DNA. Complexes 7–12 may undergo an intercalative mode of binding due to their structural differences relative to 1–6. The intrinsic binding constants obtained for complexes 7–12 were also significantly varied due to their structure and binding mode ([Formula: see text] and [Formula: see text] M[Formula: see text] for complexes, 1–3 and 4–6, respectively). However, complexes 7–9 have shown much stronger binding constants ([Formula: see text] M[Formula: see text]) due to their existing planarity which leads them to strong intercalation than their counterparts, 10–12 ([Formula: see text] M[Formula: see text]). The significantly higher binding constant values for complexes 1–3 may due to their planar structure and also may possibly lead to intercalation. Though all these complexes (1–12) have shown almost similar binding constants (1.26–2.0) in the electrochemical analysis, it implies that these complexes interact towards DNA with equal strength at their reduced oxidation (M[Formula: see text]) states. The obtained results in various spectral, electrochemical, relative viscosity changes, DNA cleavage studies revealed that these complexes 1–6 mimic the functional properties of cisplatin. Therefore, these nanostructured complexes could be substituted for cisplatin as a new family of non-platinum-based anticancer drugs in the future, after a sequence of in-vivo investigation. Their potential activity against A549 cancer cells has also been recorded using Hoechst staining and Propidium iodide images.

Polyamines (PAs) but not small peptides with closely spaced positively charged groups interact with DNA and RNA, but they do not represent a relevant buffer system at physiological pH values.

Polyamines (PAs) including putrescine (PUT), spermidine (SPD) and spermine (SPM) are small, versatile molecules with two or more positively charged amino groups. Despite their importance for almost all forms of life, their specific roles in molecular and cellular biology remain partly unknown. The molecular structures of PAs suggest two presumable biological functions: (i) as potential buffer systems and (ii) as interactants with poly-negatively charged molecules like nucleic acids. The present report focuses on the question, whether the molecular structures of PAs are essential for such functions, or whether other simple molecules like small peptides with closely spaced positively charged side chains might be suitable as well. Consequently, we created titration curves for PUT, SPD, and SPM, as well as for oligolysines like tri-, tetra-, and penta-lysine. None of the molecules provided substantial buffering capacity at physiological intracellular pH values. Apparently, the most important mechanism for intracellular pH homeostasis in neurons is not a buffer system but is provided by the actions of the sodium-hydrogen and the bicarbonate-chloride antiporters. In a similar approach we investigated the interaction with DNA by following the extinction at 260 nm when titrating DNA with the above molecules. Again, PUT and tri-lysine were not able to interact with herring sperm DNA, while SPD and SPM were. Obviously, the presence of several positively charged groups on its own is not sufficient for the interaction with nucleic acids. Instead, the precise spacing of these groups is necessary for biological activity.

Unlabelled LRET biosensor based on double-stranded DNA for the detection of anthraquinone anticancer drugs.

Based on upconversion nanoparticles (UCNPs) as energy donor and herring sperm DNA (hsDNA) as molecular recognition element, an unlabelled upconversion luminescence (UCL) affinity biosensor was constructed for the detection of anthraquinone (AQ) anticancer drugs in biological fluids. AQ anticancer drugs can insert into the double helix structure of hsDNA on the surface of UCNPs, thereby shortening the distance from UCNPs. Therefore, the luminescence resonance energy transfer (LRET) phenomenon is effectively triggered between UCNPs and AQ anticancer drugs. Hence, AQ anticancer drugs can be quantitatively detected according to the UCL quenching rate. The biosensor showed good sensitivity and stability for the detection of daunorubicin (DNR) and doxorubicin (ADM). For the detection of DNR, the linear range is 1-100 μg·mL-1 with a limit of detection (LOD) of 0.60 μg·mL-1, and for ADM, the linear range is 0.5-100 μg·mL-1 with a LOD of 0.38 μg·mL-1. The proposed biosensor provides a convenient method for monitoring AQ anticancer drugs in clinical biological fluids in the future.

Research on the Interaction between AP and Herring Sperm DNA

Research on the Interaction between AP and Herring Sperm DNA

Electrospun composite nanofibers of deoxyribonucleic acid and polylactic acid for skincare applications.

The development of useful biomaterials has resulted in significant advances in various fields of science and technology. The demand for new biomaterial designs and manufacturing techniques continues to grow, with the goal of building a sustainable society. In this study, two types of DNA-cationic surfactant complexes were synthesized using commercially available deoxyribonucleic acid from herring sperm DNA (hsDNA, <50 bp) and deoxyribonucleic acid from salmon testes DNA (stDNA, ~2000 bp). The DNA-surfactant complexes were blended with a polylactic acid (PLA) biopolymer and electrospun to obtain nanofibers, and then copper nanoparticles were synthesized on nanofibrous webs. Scanning electron microscopic images showed that all nanofibers possessed uniform morphology. Interestingly, different diameters were observed depending on the base pairs in the DNA complex. Transmission electron microscopy showed uniform growth of copper nanoparticles on the nanofibers. Fourier-transform infrared spectroscopy spectra confirmed the uniform blending of both types of DNA complexes in PLA. Both stDNA- and hsDNA-derived nanofibers showed greater biocompatibility than native PLA nanofibers. Furthermore, they exerted significant antibacterial activity in the presence of copper nanoparticles. This study demonstrates that DNA is a potentially useful material to generate electrospun nanofibrous webs for use in biomedical sciences and technologies.

Synthesis and characterization of nanoscale level mono/bi-ligated metal(II) complexes

A series of nanoscale level metal complexes with bidentate (N2MCl2) and tetradentate (MN) chromophores as cisplatin analogues and intercalating agents of, [M(phen)Cl2] (1- 3), [M(bpy)Cl2] (4-6), [M(phen)2] (7-9) and [M(bpy)2] (10-12) (where respectively M = Cu(II), Ni(II) or Zn(II); phen = 1,10-phenanthroline and bpy = 2,2’-bipyridine) respectively were prepared in the present investigation. These complexes were prepared by sonochemical technique and characterized using elemental, spectral, and electrochemical techniques. Their nanorod or stick morphologies and crystalline nature were evaluated with scanning electron microscopy (SEM). Metal complexes, 1-6 are existing with two labile chlorides similar to the chemotherapeutic inorganic drug cisplatin, which may anticipate binding covalently with herring sperm DNA, While, complexes, 7-12 may undergo an intercalative mode of binding due to their structural differences relative to 1-6.

Insights into the intercalative binding of benzo[b]fluoranthene with herring sperm DNA in vitro and its application

Benzo[b]fluorathene (BbF) is one of common polycyclic aromatic hydrocarbons with strong carcinogenic and teratogenic properties and mutagenicity in the environment. In this work, the mechanism underlying the relationship between BbF and herring sperm DNA (hs–DNA) in vitro under simulated physiological conditions was studied through multi-spectroscopic approaches (fluorescence spectroscopy, UV–Vis spectroscopy, resonance scattering spectra, and circular dichroism) coupled with agarose gel electrophoresis, fluorescence microscopy, and viscosity measurements. UV–vis and fluorescence spectra results showed that the BbF–DNA complexes formed with a binding constant of 8.95 ± 0.19 × 105 L/mol, and BbF bound to DNA by intercalative binding. These findings were further confirmed through circular dichroism, potassium iodide quenching experiment, salt ion effect tests, and viscosity measurement. Obtained from the resonance scattering spectral data, the saturation value of DNA with BbF was 2.4, revealing that BbF may cause DNA damage. The thermodynamic parameters revealed that the binding process was entropically driven by the spontaneous reaction between BbF and DNA. The main stabilizing forces between BbF and DNA were van der Waals force and π-π packing. Agarose gel electrophoresis and fluorescence microscopy results intuitively verified that the interaction mode of BbF and DNA was intercalation. Moreover, on the basis of intercalative binding between BbF and DNA, DNA and magnetic beads were used to selectively capture BbF, and the removal rate of BbF was 98.76%. This study provides mechanisms underlying the toxicity of BbF and novel insights into BbF clearance methods based on BbF–DNA intercalation.

Syntheses and high selective cytotoxicity of dehydroabietylamine C-ring nitration derivatives

To find more effective anticancer agents, a series of novel dehydroabietylamine (DA) derivatives were synthesized, focusing on C-ring nitro modifications and C-18 imide introduction. Their cytotoxic activities against human tumor cell line HeLa (cervix), MCF-7 (breast), A549 (lung), HepG2 (liver), and nonmalignant cell line HUVEC (umbilical vein) in vitro were screened. The C-18 imide heterocyclic compounds 1, 2, and C-ring 14-nitro substituted 14 exhibited moderate to good cytotoxic activities and significant selectivity towards malignant cell lines. More importantly, they were significantly less cytotoxic to nonmalignant cells (HUVEC) than the parent compound and positive control doxorubicin hydrochloride (DOX). Meantime the mechanism of cytotoxicity of DA derivatives was studied. Annexin V-FITC/PI double-staining analysis suggested that cytotoxicity of compounds 2 and 14 was associated with early apoptosis induction. The interaction between compounds and DNA (herring sperm DNA) was studied using absorption spectral analysis and ethidium bromide (EB) fluorescence displacement experiments, the results exhibited that the binding of the compound to DNA was in the intercalative mode. The structure-activity relationship discussion implied that introduction of the nitro-group, especially the 14-nitro group, can significantly improve the cytotoxicity of dehydroabietylimide compounds. The relatively high cytotoxicity and significant high selectivity of compounds 2 and 14 indicated that they were particularly noteworthy. NO released amounts indicated that the amounts of NO released by the compounds bearing nitro-group were quite well associated positive correlation with their cytotoxic activity, which provide a new strategy for structure design of DA anticancer agents in the future.

Feeding Brassica vegetables to rats leads to the formation of characteristic DNA adducts (from 1-methoxy-3-indolylmethyl glucosinolate) in many tissues

Juices of Brassica vegetables are mutagenic and form characteristic DNA adducts in bacteria and mammalian cells. In this study, we examined whether such adducts are also formed in vivo in animal models. Rats fed raw broccoli ad libitum in addition to normal laboratory chow for 5 weeks showed one major adduct spot and sometimes an additional minor adduct spot in liver, kidney, lung, blood and the gastrointestinal tract, as determined by 32P-postlabelling/thin-layer chromatography. Adducts with the same chromatographic properties were formed when herring sperm DNA (or dG-3’-phosphate) was incubated with 1-methoxy-3-indolylmethyl glucosinolate (phytochemical present in Brassica plants), in the presence of myrosinase (plant enzyme that hydrolyses glucosinolates to bioactive breakdown products). UPLC–MS/MS analysis corroborated this finding: 1-Methoxy-3-indolylmethyl-substituted purine nucleosides were detected in the hepatic DNA of broccoli-fed animals, but not in control animals. Feeding raw cauliflower led to the formation of the same adducts. When steamed rather than raw broccoli was used, the adduct levels were essentially unchanged in liver and jejunum, but elevated in large intestine. Due to inactivation of myrosinase by the steaming, higher levels of the glucosinolates may have reached the large bowl to be activated by glucosidases from intestinal bacteria. In conclusion, the consumption of common Brassica vegetables can lead to the formation of substantial levels of DNA adducts in animal models. The adducts can be attributed to a specific phytochemical, neoglucobrassicin (1-methoxy-3-indolylmethyl glucosinolate).

Synthesis, characterization, DNA binding, antibacterial, antidiabetic, molecular docking and DFT studies of Ni(II), Cu(II) and Zn(II) complexes derived from heterocyclic schiff base

Novel metal complexes of nickel(II), copper(II) and zinc(II) have been synthesized and characterized. DFT‐based molecular orbital energy calculations of the synthesized ligand and metal complexes have been studied. Ligand and its complexes were screened for their antibacterial activities by disk diffusion method. The quantitative antimicrobial activity of the test compounds was evaluated using Resazurin based Microtiter Dilution Assay. The interaction of these complexes with Herring sperm DNA (HS-DNA) was analyzed via UV–Visible absorption, circular dichroism and Voltammetric studies, which indicates that these complexes bind to HS-DNA by intercalation binding mode. Molecular docking was also used to identify the interaction between ligand and complexes with DNA. α-Amylase inhibition activity of ligand its metal complexes has been determined by DNS method. Kinetic studies were carried out to identify the mode of inhibition using Lineweaver-Burk plot. The cytotoxicity of these metal complexes has been evaluated by MTT assay against normal 3T3L1 cells.

Knockout of MAPK Phosphatase-1 Exaggerates Type I IFN Response during Systemic Escherichia coli Infection.

We have previously shown that Mkp-1-deficient mice produce elevated TNF-α, IL-6, and IL-10 following systemic Escherichia coli infection, and they exhibited increased mortality, elevated bacterial burden, and profound metabolic alterations. To understand the function of Mkp-1 during bacterial infection, we performed RNA-sequencing analysis to compare the global gene expression between E. coli-infected wild-type and Mkp-1 -/- mice. A large number of IFN-stimulated genes were more robustly expressed in E. coli-infected Mkp-1 -/- mice than in wild-type mice. Multiplex analysis of the serum cytokine levels revealed profound increases in IFN-β, IFN-γ, TNF-α, IL-1α and β, IL-6, IL-10, IL-17A, IL-27, and GMSF levels in E. coli-infected Mkp-1 -/- mice relative to wild-type mice. Administration of a neutralizing Ab against the receptor for type I IFN to Mkp-1 -/- mice prior to E. coli infection augmented mortality and disease severity. Mkp-1 -/- bone marrow-derived macrophages (BMDM) produced higher levels of IFN-β mRNA and protein than did wild-type BMDM upon treatment with LPS, E. coli, polyinosinic:polycytidylic acid, and herring sperm DNA. Augmented IFN-β induction in Mkp-1 -/- BMDM was blocked by a p38 inhibitor but not by an JNK inhibitor. Enhanced Mkp-1 expression abolished IFN-β induction by both LPS and E. coli but had little effect on the IFN-β promoter activity in LPS-stimulated RAW264.7 cells. Mkp-1 deficiency did not have an overt effect on IRF3/7 phosphorylation or IKK activation but modestly enhanced IFN-β mRNA stability in LPS-stimulated BMDM. Our results suggest that Mkp-1 regulates IFN-β production primarily through a p38-mediated mechanism and that IFN-β plays a beneficial role in E. coli-induced sepsis.

Biodegradation efficacy of coke oven wastewater inherent co-cultured novel sp. Alcaligenes faecalis JF339228 and Klebsiella oxytoca KF303807 on phenol and cyanide—kinetic and toxicity analysis

Coke oven sector emanates phenol and cyanide as the eminent virulent compounds due to abrupt industrialization which is detrimental in aqueous state, and its severity is increased on simultaneous coexistence even at low concentrations that eventually causes extensive damage to the peripheral ecosystem. The efficacy of isolated mixed bacterial culture comprising of Alcaligenes faecalis JF339228 and Klebsiella oxytoca KF303807 in wastewater treatment was investigated following a batch study. The impact of initial concentration of phenol (100–1500 mg L−1) and cyanide (10–150 mg L−1) on the growth and treatment by the mixed microbial cultures were evaluated over a time period of 72 h. The biodegradation mechanism was explained by Monod, Haldane, Aiba and Edward kinetic models. The maximum specific growth rate was reported to be 0.096 h−1 and 0.126 h−1 for phenol and cyanide respectively. The substrate inhibitory effect became eminent after a concentration of 450 mg L−1 for phenol and 45 mg L−1 for cyanide. Based on the lower sum of squared error (SSE) values, Haldane model for phenol and Edward model for cyanide was found to be favourable for substrate inhibition kinetics. The fate of the secondary intermediates produced after microbial degradation was assessed by phytotoxicity studies using Vigna radiata. The interactive binding of the pernicious pollutants and resultant biodegraded compounds with the DNA (herring sperm DNA) was examined following spectrofluorometric and spectrophotometric anatomization. Toxicity studies revealed that biological treatment was viable for eco benign disposal and results also depicted that both the strains have potential in remediation of phenol and cyanide from coke oven wastewater.

Antiproliferative and Pro-Apoptotic Effects of Thiazolo[3,2-b][1,2,4]triazoles in Breast and Cervical Cancer Cells.

Cancer is one of the leading causes of death in the world affecting millions of people. The commercially available anticancer drugs lack the selectivity and show several undue side effects during the biologically targeted therapy, thus calling for the exploration of wider chemical space to furnish new structural leads with promising anticancer potential. In this endeavor, we synthesized a series of coumarinyl thiazolotriazoles with diverse functional group tolerance and will be tested for their anticancer properties against cancer cell lines (HeLa and MCF-7) and a normal cell line (BHK-21). To overcome such complications, in the current study, we evaluated the cytotoxic effects of coumarinyl thiazolotriazole hybrids on human breast adenocarcinoma (MCF-7), cervical adenocarcinoma (HeLa) cells and normal cells i.e., Baby Hamster Kidney cells (BHK-21) using MTT (dimethyl-2-thiazolyl- 2,5-diphenyl-2H-tetrazolium bromide) assay. DNA binding studies of compound 6c was performed on Herring- Sperm DNA (HS-DNA) and docking studies were also carried out. The mechanistic studies were performed on potent compounds by fluorescent microscopic studies, release of Lactate Dehydrogenase (LDH) and mitochondrial membrane potential, activation of caspase-9 and -3 and flow cytometric analysis. As revealed by MTT assay, compounds 6m and 6c were identified as the most potent derivatives among the tested series with IC50 values of 5.64 and 29.1 μM against HeLa and MCF cells, respectively as compared to cisplatin which gave IC50 values of 11.3 and 6.20 μM, respectively. DNA binding studies of compound 6c showed the binding of compound in DNA with Gibbs free energy of ‒17 KJ/mol and docking studies validated the DNA binding studies. Fluorescent microscopic studies using 4',6-diamidino-2-phenylindole (DAPI) and Propidium Iodide (PI) staining confirmed the occurrence of apoptosis in HeLa cells treated with the most active compound 6m. Moreover, compounds 6m and 6c also triggered the release of Lactate Dehydrogenase (LDH) in treated HeLa and MCF-7 cells while a luminescence assay displayed a remarkable increase in the activity of caspase-9 and -3. Moreover, flow cytometric results revealed that compound 6m caused G0 /G1 arrest in the treated HeLa cells. Our results suggested that the compound possesses chemotherapeutic properties against breast cancer and cervical adenocarcinoma cells, thus warranting further research to test the anticancer efficacy of this compound at clinical level.

Influence of cationic surfactant cetyltrimethylammonium bromide for electrochemical detection of guanine, uric acid and dopamine

Frontier molecular orbital and analytical Fukui functions were used to theoretically study cationic surfactant cetyltrimethylammonium bromide (CTAB), predicting its capability for sensitive detection of guanine (GU), uric acid (UA), and dopamine (DA). Herein, we fabricated the CTAB-modified carbon paste electrode (CTCPE), and it exhibited improved sensitivity for the simultaneous detection of three biomolecules, GU, UA, and DA due to the active sites of the CTAB molecules on the electrode surface, which is also proved by our theoretical studies. The CTCPE was used to effectively analyze the various concentration of biomolecules in the mixture containing GU, UA, and DA. The lowest detection limits for the linear range of GU (2–60 μM), UA (5–125 μM), and DA (1–70 μM) have been found to be 0.3, 1.7, and 0.2 μM, respectively. For the detection of target molecules in real samples, such as herring sperm DNA, DA injection, and human blood serum, the CTCPE shows considerably good performance. In our studies, the CTCPE demonstrates good repeatability, stability, and selectivity for detecting GU, UA, and DA with high sensitivity.

Development of a high cell density transient CHO platform yielding mAb titers greater than 2 g/L in only 7 days.

We developed a simple transient Chinese Hamster Ovary expression platform. Titers for a random panel of 20 clinical monoclonal antibodies (mAbs) ranged from 0.6 to 2.7 g/L after 7 days. Two factors were the key in obtaining these high titers. First, we utilized an extremely high starting cell density (20 million cells/ml), and then arrested further cell growth by employing mild hypothermic conditions (32°C). Second, we performed a 6-variable Design of Experiments to find optimal concentrations of plasmid DNA (coding DNA), boost DNA (DNA encoding the XBP1S transcription factor), transfection reagent (polyethylenimine [PEI]), and nutrient feed amounts. High coding DNA concentrations (12.5 mg/L) were found to be optimal. We therefore diluted expensive coding DNA with inexpensive inert filler DNA (herring sperm DNA). Reducing the coding DNA concentration by 70% from 12.5 to 3.75 mg/L did not meaningfully reduce mAb titers. Titers for the same panel of 20 clinical mAbs ranged from 0.7 to 2.2 g/L after reducing the coding DNA concentration to 3.75 mg/L. Finally, we found that titer and product quality attributes were similar for a clinical mAb (rituximab) expressed at very different scales (volumes ranging from 3 ml to 2 L).

Poly (alanine)/NaOH/ MoS2/MWCNTs modified carbon paste electrode for simultaneous detection of dopamine, ascorbic acid, serotonin and guanine

The detection of biomolecules such as dopamine (DA), ascorbic acid (AA), serotonin (5-HT), and guanine (GU) is essential for biomedical chemistry and disease diagnosis. In this work, MoS2/acid-treated MWCNTs composite (Ms-atCNTs) was first prepared and then used to modify carbon paste electrode (CPE), followed by electropolymerization of alanine in the presence of NaOH. The resulting modified electrode (p-Aln/Ms-atCNTCPE) was tested for the simultaneous detection of DA, AA, 5-HT, and GU using cyclic voltammetry and differential pulse voltammetry in phosphate buffer solution (PBS). The p-Aln/Ms-atCNTCPE showed excellent electrochemical response towards the detection of DA, AA, 5-HT, and GU. The electrode was also effectively utilized for concentration variation studies of a mixture containing these biomolecules. The detection limits were found to be 0.08 μM, 3.9 μM, 0.1 μM, and 0.1 μM for DA, AA, 5-HT, and GU, respectively. Furthermore, the proposed sensor displayed favorable repeatability, stability, and selectivity, as well as the usefulness for the detection of target molecules in real samples, such as DA injections, vitamin C tablets, herring sperm DNA, and human blood serum.

Evaluation of the effect of Tb(IV)-NR complex on herring sperm DNA genetic information by mean of spectroscopic

The interaction between Tb(IV)-NR complex and herring sperm DNA in buffer solution of Tris-HCl was investigated with the use of acridine orange(AO) as a spectral probe. The binding modes and other information were provided by the UV–spectrophotometry and fluorescence spectroscopy. The thermodynamic functions expressed that the binding constants of Tb(IV)-NR complex with DNA was Kθ298.15K = 4.03 × 105 L·mol−1, Kθ310.15K =1.30 × 107 L·mol−1, and the ΔrGθ m 298.15 K＝−3.20 × 104 J·mol−1. The scatchard equation suggested that the interaction mode between Tb(IV)-NR complex and herring sperm DNA is electrostatic and weak intercalation bindings. FTIR spectroscopy results also indicate that there is a specific interaction between the Tb(IV)-NR complex and the A and G bases of DNA.

Synthesis, DNA/BSA binding studies and in vitro biological assay of nickel(II) complexes incorporating tridentate aroylhydrazone and triphenylphosphine ligands

Two new nickel (II) triphenylphosphine complexes derived from tridentate aroylhydrazone ligands [H2L1 = 2-hydroxy-3-methoxybenzylidene)benzohydrazone and H2L2 = N′-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazone] and triphenylphosphine were prepared and their molecular structures were determined by single crystal X-ray diffraction analysis. Both nickel(II) complexes showed slightly distorted square planar geometry with one tridentate aroylhydrazone ligand coordinated through ONO donor atoms and one triphenylphosphine ligand coordinated to the nickel center through the phosphorus atom. DNA interaction studies indicated that both complexes possessed higher affinity to herring sperm DNA (HS-DNA) than the corresponding free aroylhydrazone ligand. Molecular docking investigations showed that both complexes could bind to DNA through intercalation of the phenyl rings between adjacent base pairs in the double helix. Meanwhile, bovine serum albumin (BSA) binding studies revealed the complexes could effectively interact with BSA and change the secondary structure of BSA. Further pharmacological evaluations of the synthesized complexes by in vitro antioxidant assays demonstrated high antioxidant activity against NO· and O2˙− radicals. The anticancer activity of each complex was assessed through in vitro cytotoxicity assays (CCK-8 kit) toward A549 and MCF-7 cancer cell and normal L-02 cell lines. Significantly, the Ni(II) complex derived from H2L1 ligand was found to be more effective cytotoxic toward MCF-7cancerous cell with the IC50 value equaled 9.7 μM, which showed potent cytotoxic activity over standard drug cisplatin. AbbreviationsA549human lung carcinoma cellBSAbovine serum albuminCCK-8Cell Counting Kit-8DFTdensity functional theoryDNAdeoxyribonucleic acidDPPH˙2,2-diphenyl-1-picrylhydrazylH2L12-hydroxy-3-methoxybenzylidene)benzohydrazone N′-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazoneH2L2N′-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazoneHOMOhighest occupied molecular orbitalIC50the 50% activityL-02human normal liver cellLOMOlowest unoccupied molecular orbital (LUMO)MCF-7human breast carcinoma cellNO˙nitric oxideO2˙−superoxide anionSODsuperoxide dismutaseCommunicated by Ramaswamy H. Sarma

Cytoplasmic RNA Sensor Pathways and Nitazoxanide Broadly Inhibit Intracellular Mycobacterium tuberculosis Growth.

SummaryTo establish stable infection, Mycobacterium tuberculosis (MTb) must overcome host innate immune mechanisms, including those that sense pathogen-derived nucleic acids. Here, we show that the host cytosolic RNA sensing molecules RIG-I-like receptor (RLR) signaling proteins RIG-I and MDA5, their common adaptor protein MAVS, and the RNA-dependent kinase PKR each independently inhibit MTb growth in human cells. Furthermore, we show that MTb broadly stimulates RIG-I, MDA5, MAVS, and PKR gene expression and their biological activities. We also show that the oral FDA-approved drug nitazoxanide (NTZ) significantly inhibits intracellular MTb growth and amplifies MTb-stimulated RNA sensor gene expression and activity. This study establishes prototypic cytoplasmic RNA sensors as innate restriction factors for MTb growth in human cells and it shows that targeting this pathway is a potential host-directed approach to treat tuberculosis disease.