Calf Thymus Research Articles

A combined physicochemical and computational investigation of the inclusion behaviour of 3-(1-Naphthyl)-D-alanine Hydrochloride insights into β-Cyclodextrin

In numerous biological activities, 3-(1-Naphthyl)-D-alanine Hydrochloride (D-1NA) serves as an essential metabolic precursor and amino acid receptor. Therefore, a sufficient supply of D-1NA is very much important. Here, we look into how D-1NA interacts with the hydrophobic cavity of β-cyclodextrin (BCD) to form the host–guest assembly. Analysis of experimental and theoretical findings demonstrates the creation of a stable IC, which is suggestive of the usefulness of BCD as a delivery method for D-1NA. The binding behaviour of this newly created 1:1 inclusion system of D-1NA with BCD has been examined by UV–visible spectroscopy and discovered that BCD showed a considerable affinity for D-1NA and the binding process was thermodynamically possible. Molecular docking analysis demonstrated the most reliable D-1NA binding orientation inside the BCD, as shown by Fourier transforms infrared and 1H-Nuclear magnetic resonance spectroscopic analyses. Studies using PXRD and SEM images also showed that inclusion complexes had formed. After complexing with BCD, D-1NA's photostability is increased. Additionally, it was described how the produced IC is bound to the Deoxyribonucleic acid (DNA) of the calf thymus (CT).

Revealing the effects of ligands of silver nanoclusters on the interactions between them and ctDNA: Abstraction to visualization

Silver nanoclusters (AgNCs) have been widely applied in the field of biology, drug therapy and cell imaging in the last decade. In order to study the biosafety of AgNCs, GSH-AgNCs and DHLA-AgNCs were synthesized using glutathione (GSH) and dihydrolipoic acid (DHLA) as ligands, and their interactions with calf thymus DNA (ctDNA) from abstraction to visualization were studied. The results of spectroscopy, viscometry and molecular docking demonstrated that GSH-AgNCs mainly bound to ctDNA in a groove mode, while DHLA-AgNCs were both groove and intercalation binding. Fluorescence experiments suggested that the quenching mechanism of both AgNCs to the emission of ctDNA-probe were both in static mode, and thermodynamic parameters demonstrated that the main forces between GSH-AgNCs and ctDNA were hydrogen bonds and van der Waals forces, while hydrogen bonds and hydrophobic forces contributed to the binding of DHLA-AgNCs to ctDNA. The binding strength demonstrated that DHLA-AgNCs bound to ctDNA more strongly than that of GSH-AgNCs. The results of circular dichroism (CD) spectroscopy reflected small effects of both AgNCs on the structure of ctDNA. This study will support the theoretical foundation for the biosafety of AgNCs and have a guiding significance for the preparation and application of AgNCs.

Structural and Biological Properties of Heteroligand Copper Complexes with Diethylnicotinamide and Various Fenamates: Preparation, Structure, Spectral Properties and Hirshfeld Surface Analysis

Herein, we discuss the synthesis, structural and spectroscopic characterization, and biological activity of five heteroligand copper(II) complexes with diethylnicotinamide and various fenamates, as follows: flufenamate (fluf), niflumate (nifl), tolfenamate (tolf), clonixinate (clon), mefenamate (mef) and N, N-diethylnicotinamide (dena). The complexes of composition: [Cu(fluf)2(dena)2(H2O)2] (1), [Cu(nifl)2(dena)2] (2), [Cu(tolf)2(dena)2(H2O)2] (3), [Cu(clon)2(dena)2] (4) and [Cu(mef)2(dena)2(H2O)2] (5), were synthesized, structurally (single-crystal X-ray diffraction) and spectroscopically characterized (IR, EA, UV-Vis and EPR). The studied complexes are monomeric, forming a distorted tetragonal bipyramidal stereochemistry around the central copper ion. The crystal structures of all five complexes were determined and refined with an aspheric model using the Hirshfeld atom refinement method. Hirshfeld surface analysis and fingerprint plots were used to investigate the intermolecular interactions in the crystalline state. The redox properties of the complexes were studied and evaluated via cyclic voltammetry. The complexes exhibited good superoxide scavenging activity as determined by an NBT assay along with a copper-based redox-cycling mechanism, resulting in the formation of ROS, which, in turn, predisposed the studied complexes for their anticancer activity. The ability of complexes 1–4 to interact with calf thymus DNA was investigated using absorption titrations, viscosity measurements and an ethidium-bromide-displacement-fluorescence-based method, suggesting mainly the intercalative binding of the complexes to DNA. The affinity of complexes 1–4 for bovine serum albumin was determined via fluorescence emission spectroscopy and was quantitatively characterized with the corresponding binding constants. The cytotoxic properties of complexes 1–4 were studied using the cancer cell lines A549, MCF-7 and U-118MG, as well as healthy MRC-5 cells. Complex 4 exhibited moderate anticancer activity on the MCF-7 cancer cells with IC50 = 57 μM.

Catalytic potential of sustainable dinuclear (Cu2+ and ZrO2+) metal organic incorporated frameworks with comprehensive biological studies

BackgroundThe high coordination ability of dihydrazone derivatives with metals of different valents, new homo dinuclear complexes of low and high valent ions of Cu2+ and ZrO2+ (CuLss and ZrOLss, respectively) were constructed via their coordination with diisatin succinyldihydrazone ligand (H2Lss). In which, the structure confirmation of H2Lss and its MLss complexes were achieved by different distinguished spectral tools. MethodsThe two novel MLss complexes were constructed by 2: 1 molar amounts of M2+ (Cu2+ or ZrO2+) ion to the H2Lss mole in DMF. Their catalytic action was examined under aerobic and homogeneous phase in the productive benzyl alcohol redox protocol within an aqueous H2O2. The antimicrobial and anticancer activities of H2Lss, CuLss and ZrOLss were investigated. In addition, their interaction with calf thymus DNA (ctDNA) was studied through spectrophotometric and viscometric techniques. The significant findingsAppreciable productivity was recognized with the yielded amounts of benzaldehyde (the corresponded selective oxide product) with both catalysts. However, CuLss represents more classified action by 92% yielding of benzaldehyde (for about 5 h at reaction temperature 60 °C with 0.005 mmol of its loaded amount), whereas, ZrOLss showed less efficacy with 87% (for 3 h at temperature of the reaction 70 °C with 0.005 mmol loaded amount). The catalytic progress referred to the nature of metal ion, which could be interpreted in the catalytic mechanism, i.e. the oxygen transfer pathway. The two MLss complexes exhibited more significant inhibiting affect against the bacterial and fungal strains and as well as the cancer cell lines than those of the free H2Lss, pointing to the function of M2+ ion in their MLss complexes. CuLss showed more interaction potential with ctDNA more than that of ZrOLss according to the Kb, the binding constants, (= 16.51 and 14.37 × 107 mol−1.dm3), also on the derived values of the Gibbs’ free energy values (ΔGb≠ = -46.39 and -45.61 kJ.mol−1), respectively, however, both CuLss and VOLss exhibited higher reactivity over their H2Lss (Kb = 10.87 × 107 mol−1.dm3 and ΔGb≠ = -43.75 kJ.mol−1) referring to the type and nature of interaction depending on the M2+ ion to progress their reactivity towards ctDNA.

Crystal structure, fluorescence, magnetic properties and DNA interaction of four novel binuclear LnⅢ2 compounds with Schiff ligand

Four new Ln2 compounds, [Ln2(H2L−)2(acac)2(CH3O)2] (Ln = Sm(1), Tb(2), Ho(3) and Er(4), H3L = 2‑hydroxy-N’-[(1E)-(8-hydroxyquinolin-2-yl)methylidene]benzohydrazide), were synthesized by using a multidentate Schiff ligand and lanthanide β-diketone salts via solvent evaporation methods. The X-ray structural analysis reveal that the four Ln2 compounds are dinuclear compounds and each Ln(Ⅲ) ion is eight-coordinated. The two central Ln(Ⅲ) ions are bridged by two μ2O atoms from 8-hydroxyquinoline Schiff base ligands, leading to a parallelogram Ln2O2 core. The magnetism investigation shows that compound 2 display slow magnetic relaxation behavior under zero dc field (ΔE/kB = 19.77 K and τ0 = 1.35 × 10−6 s). Subsequent studies strongly suggested that the four Ln2 compounds binded to Calf thymus DNA (CT-DNA) through intercalative mode and have pBR322 plasmid DNA cleavage ability. This work will provide more insights for the design and investigation of lanthanide-based SMMs, and has certain reference value to study the interaction between compound and DNA.

DNA-functionalized carbon quantum dots for electrochemical detection of pyocyanin: A quorum sensing molecule in Pseudomonas aeruginosa

The electrochemical biosensing strategy for pyocyanin (PYO), a virulent quorum-sensing molecule responsible for Pseudomonas aeruginosa infections, was developed by mimicking its extracellular DNA interaction. Calf thymus DNA (ct-DNA) functionalized amine-containing carbon quantum dots (CQDs) were used as a biomimetic receptor for electrochemical sensing of PYO as low as 37 nM in real urine sample. The ct-DNA-based biosensor enabled the selective measurement of PYO in the presence of other interfering species. Calibration and validation of the PYO sensor platform were demonstrated in buffer solution (0–100 μM), microbial culture media (0–100 μM), artificial urine (0–400 μM), and real urine sample (0–250 μM). The sensor capability was successfully implemented for point-of-care (POC) detection of PYO release from Pseudomonas aeruginosa strains during lag and stationary phases. Cross-reactivity of the sensing platform was also tested in other bacterial species such as Bacillus subtilis, Escherichia coli, Klebsiella pneumoniae, Shigella dysenteriae, Staphylococcus aureus, and Streptococcus pneumoniae. Potential clinical implementation of the ct-DNA-based sensor was manifested in detecting the PYO in P. aeruginosa cultured baby diaper and sanitary napkin. Our results highlight that the newly developed ct-DNA-based sensing platform can be used as a potential candidate for real-time POC diagnosis of Pseudomonas aeruginosa infection in clinical samples.

Theoretical study of C6F5-corrole molecules functionalized with aromatic groups for Photodynamic Therapy

The singlet oxygen generation by electronically excited molecules in photodynamic therapy (PDT) requires light absorption within a specific wavelength window, and a subsequent intersystem crossing transition to a triplet excited state that is, at least, 0.98 eV higher in energy than the singlet ground state. Tetrapyrrolic macrocycles, such as porphyrin and corrole, have been widely used in oxygen singlet generation for PDT. Suitable functionalization can potentialize these macrocycles as photosensitizers. In this contribution, we use Density Functional Theory (DFT) calculations to determine the structural, electronic and spectroscopic properties of corrole macrocycles bound to different polycyclic aromatic groups in the gas phase, dichloromethane, and water. We also calculate the spin–orbit coupling (SOC) matrix elements of the intersystem crossing channels involving the first excited singlet states and excited triplet states. The results for optical absorption show that the threshold wavelength for optical absorption increases with the polarity of the environment and the number of aromatic rings of the ligands, whereas the oscillator strengths increase with the polarity of the environment but decrease with the number of aromatic rings. It is verified that the triplet excited states involved in the intersystem crossing transitions satisfy the energy requirement for the oxygen singlet generation. The magnitude of spin–orbit coupling (SOC) matrix elements associated with the intersystem crossing are also seen to be dependent on the environment involving the corrole molecules, and on the number of aromatic rings of the ligands connected to the corrole. Further, the binding of the functionalized corrole molecules with biomolecules as the calf thymus DNA and human serum albumin is studied and characterized through molecular docking. These results show that the corrole macrocycles, suitably functionalized with polycyclic aromatic groups, fulfill several criteria to be considered as good PDT photosensitizers.

DNA groove binder and significant cytotoxic activity on human colon cancer cells: Potential of a dimeric zinc (II) phthalocyanine derivative

The interaction of a multi-component system consisting of benzene-1,4-diyldimethanimine-bridged dimeric zinc-phthalocyanine groups (4OMPCZ) with calf thymus DNA (ct-DNA) was investigated using UV–Vis absorption, fluorescence emission spectroscopy methods, and viscosity measurements. The binding constant, Kb, which is an important parameter to gain information about the binding mode, was found as 9.7 × 107 M−1 from the UV–Vis absorption studies. Another important spectrophotometric tool is competitive displacement assays with Ethidium bromide and Hoechst 33342. Through this experiment, a higher KSV value was obtained with Hoechst for the phthalocyanine derivative, 4OMPCZ, and the ct-DNA complex than with ethidium bromide. Additionally, molecular docking studies were conducted to calculate the theoretical binding constant and visualize the interactions of 4OMPCZ with a model DNA. According to docking results, although the interactions are mainly located in the major groove of the DNA helix, due to the wrapping, these interactions can also be extended to the minor groove of the DNA. Spectrophotometric, molecular docking, and viscosity studies revealed that the interaction of 4OMPCZ with DNA is likely to be via the major and minor grooves. The in vitro cytotoxic activity of 4OMPCZ was evaluated by MTT assay on human colon cancer cells (HT29) after 72 h of treatment. 4OMPCZ indicated significant cytotoxic activity when stimulated with UV light compared to the standard chemotherapy drugs, fluorouracil (5-FU), and cisplatin on HT29 colon cancer cells. The IC50 value of 4OMPCZ displayed considerably lower concentrations compared to the standard drugs, 5-FU, and cisplatin.

Biological Effects in Cancer Cells of Mono- and Bidentate Conjugation of Cisplatin on PAMAM Dendrimers: A Comparative Study.

Cisplatin (cis-diamminedichloroplatinum(II)) is a potent chemotherapeutic agent commonly used to treat cancer. However, its use also leads to serious side effects, such as nephrotoxicity, ototoxicity, and cardiotoxicity, which limit the dose that can be safely administered to patients. To minimize these problems, dendrimers may be used as carriers for cisplatin through the coordination of their terminal functional groups to platinum. Here, cisplatin was conjugated to half-generation anionic PAMAM dendrimers in mono- and bidentate forms, and their biological effects were assessed in vitro. After preparation and characterization of the metallodendrimers, their cytotoxicity was evaluated against several cancer cell lines (A2780, A2780cisR, MCF-7, and CACO-2 cells) and a non-cancer cell line (BJ cells). The results showed that all the metallodendrimers were cytotoxic and that the cytotoxicity level depended on the cell line and the type of coordination mode (mono- or bidentate). Although, in this study, a correlation between dendrimer generation (number of carried metallic fragments) and cytotoxicity could not be completely established, the monodentate coordination form of cisplatin resulted in lower IC50 values, thus revealing a more accessible cisplatin release from the dendritic scaffold. Moreover, most of the metallodendrimers were more potent than the cisplatin, especially for the A2780 and A2780cisR cell lines, which showed higher selectivity than for non-cancer cells (BJ cells). The monodentate G0.5COO(Pt(NH3)2Cl)8 and G2.5COO(Pt(NH3)2Cl)32 metallodendrimers, as well as the bidentate G2.5COO(Pt(NH3)2)16 metallodendrimer, were even more active towards the cisplatin-resistant cell line (A2780cisR cells) than the correspondent cisplatin-sensitive one (A2780 cells). Finally, the effect of the metallodendrimers on the hemolysis of human erythrocytes was neglectable, and metallodendrimers' interaction with calf thymus DNA seemed to be stronger than that of free cisplatin.

The interaction mechanism of candidone with calf thymus DNA: A multi-spectroscopic and MD simulation study

In this investigation, the effects of candidone on the structure and conformation of DNA were evaluated by spectroscopic methods, molecular dynamics simulation, and molecular docking studies. Fluorescence emission peaks, ultraviolet-visible spectra, and molecular docking exhibited the complex formation between candidone and DNA in a groove-binding mode. Fluorescence spectroscopy results also showed a static quenching mechanism of DNA in the presence of candidone. Moreover, thermodynamic parameters demonstrated that candidone spontaneously bound to DNA with a high binding affinity. The hydrophobic interactions were the dominant forces over the binding process. Based on the Fourier transform infrared data candidone tended to attach to the A-T base pairs of the minor grooves of DNA. The thermal denaturation and circular dichroism measurements displayed that candidone caused a slight change in the DNA structure, which was confirmed by the molecular dynamics simulation results. According to the obtained findings from the molecular dynamic simulation, the structural flexibility and dynamics of DNA were altered to a more extended structure.

A comparative study on DNA and protein binding properties of thymol and thymoquinone

Two phytochemicals, thymol and thymoquinone obtained from thymes (Thymus vulgaris L., Lamiaceae etc.) and Nagila Sativa seed, respectively. Both the phytochemicals show several biochemical activities like anticancer, antimicrobial etc. In this paper, we studied the affinities of thymol and thymoquinone towards calf thymus DNA (CT-DNA) and protein (bovine serum albumin). Spectroscopic and molecular modelling studies revealed that both compounds have a high affinity toward both the receptors; DNA and protein. Both phytochemicals binds to the minor grooves of DNA and suitable pockets of protein. Several free energy function and hydrogen bonding play significant role during the binding phenomenon. Communicated by Ramaswamy H. Sarma

Molecular Dynamics and Multi-Spectroscopic of the Interaction Behavior between Bladder Cancer Cells and Calf Thymus DNA with Rebeccamycin: Apoptosis through the Down Regulation of PI3K/AKT Signaling Pathway.

The interaction of Rebeccamycin with calf thymus (ctDNA) in the absence and presence of H1 was investigated by molecular dynamics, multi-spectroscopic, and cellular techniques. According to fluorescence and circular dichroism spectroscopies, Rebeccamycin interacted with ctDNA in the absence of H1 through intercalator or binding modes, while the presence of H1 resulted in revealing theintercalator, as the dominant role, and groove binding modes of ctDNA-Rebeccamycin complex. The binding constants, which were calculated to be 1.22 × 104M-1 and 7.92 × 105M-1 in the absence and presence of H1, respectively, denoted the strong binding of Rebeccamycin with ctDNA. The binding constants of Rebeccamycin with ct DNA in the absence and presence of H1 were calculated at 298, 303 and 308K. Considering the thermodynamic parameters (ΔH0 and ΔS0), both vander waals forces and hydrogen bonds played predominant roles throughout the binding of Rebeccamycin to ctDNA in the absence and presence of H1. The outcomes of circular dichroism suggested the lack of any major conformational changes in ctDNA upon interacting with Rebeccamycin, except some perturbations in native B-DNA at local level. Additionally, the effect of NaCl and KI on ctDNA-Rebeccamycin complex provided further evidence for the reliance of their interaction modes on substituted groups. The observed increase in the relative viscosity of ctDNA caused by the enhancement of Rebeccamycin confirmed their intercalation and groove binding modes in the absence and presence of H1. Moreover, the assessments of molecular docking simulation corroborated these experimental results and also elucidated the effectiveness of Rebeccamycinin inhibiting and proliferating T24 and 5637 cells. Meanwhile, the ability of Rebeccamycin in inhibiting cell proliferation and tumor growth through the induction of apoptosis by down regulating the PI3K/AKT signaling pathway were provided.

Evaluation of the size effect of hydrophobic ring substitution on 9-O position of berberine on DNA binding

The interaction of deoxyribonucleic acid (DNA) with medicinally significant small molecules has long piqued the interest of researchers because its applications are directly related to the discovery of new classes of drugs. Keeping this in mind, here we report berberine derivatives and their interaction with calf thymus DNA (CT-DNA). In this report we discussed on the structural perspectives and thermodynamic characteristics of the interaction of four 9-O-substituted berberines (BRDR1 to BRDR4) with CT-DNA. The binding affinity of BRDR–DNA complexes increased with increasing the cycloalkane ring size of the substitution except BRDR2. The binding constant value obtained from UV–Visible spectral analysis was 1.12 × 106 for BRDR1, 0.37 × 106 for BRDR2, 1.72 × 106 for BRDR3 and 3.20 × 106 for BRDR4. Ferrocyanide quenching experiments revealed unequivocally that the analogues except BRDR2 had a partly intercalative binding to DNA. From the ITC experiment it was found that the bindings of BRDR1, BRDR3 and BRDR4 to DNA was favoured by negative enthalpy and positive entropy while BRDR2 was driven by positive enthalpy and positive entropy. In all cases the hydrophobic interaction plays a crucial role. Thus, the complete multispectroscopic and thermodynamic binding studies may be useful for new drug design and development.Communicated by Ramaswamy H. Sarma

Erbium(III) coordination compounds with substituted salicylaldehydes: Characterization and biological profile

Five erbium(III) complexes with salicylaldehyde (saloH for 1), and mono– (5–X–saloH; X = NO2 and Me for 2 and 3, respectively) or di–substituted salicylaldehydes (3,5–diX–saloH; X = Cl and Br for 4 and 5, respectively) were synthesized and characterized by physicochemical and spectroscopic techniques and single–crystal X–ray crystallography. All five complexes have the general formula [Er(deprotonated salicylaldehyde)3(MeOH)(H2O)]. The structure of complexes [Er(3,5–diCl–salo)3(MeOH)(H2O)]·1.5MeOH (complex 4) and [Er(3,5–diBr–salo)3(MeOH)(H2O)]·1.75MeOH (complex 5) were verified by single–crystal X–ray crystallography. The evaluation of antioxidant activity of the complexes was focused on their ability to scavenge 1,1–diphenyl–picrylhydrazyl and 2,2′–azinobis–(3–ethylbenzothiazoline–6–sulfonic acid) free radicals and to reduce H2O2. The interaction of the complexes with calf–thymus DNA was investigated by UV–vis spectroscopy, viscosity measurements and via competitive studies with ethidium bromide in order to evaluate the possible DNA–binding mode and to determine the corresponding DNA–binding constants. The affinity of the complexes for bovine and human serum albumins was explored by fluorescence emission spectroscopy and the corresponding binding constants were determined.

Structural Characteristics of High-Mobility Group Proteins HMGB1 and HMGB2 and Their Interaction with DNA.

Non-histone nuclear proteins HMGB1 and HMGB2 (High Mobility Group) are involved in many biological processes, such as replication, transcription, and repair. The HMGB1 and HMGB2 proteins consist of a short N-terminal region, two DNA-binding domains, A and B, and a C-terminal sequence of glutamic and aspartic acids. In this work, the structural organization of calf thymus HMGB1 and HMGB2 proteins and their complexes with DNA were studied using UV circular dichroism (CD) spectroscopy. Post-translational modifications (PTM) of HMGB1 and HMGB2 proteins were determined with MALDI mass spectrometry. We have shown that despite the similar primary structures of the HMGB1 and HMGB2 proteins, their post-translational modifications (PTMs) demonstrate quite different patterns. The HMGB1 PTMs are located predominantly in the DNA-binding A-domain and linker region connecting the A and B domains. On the contrary, HMGB2 PTMs are found mostly in the B-domain and within the linker region. It was also shown that, despite the high degree of homology between HMGB1 and HMGB2, the secondary structure of these proteins is also slightly different. We believe that the revealed structural properties might determine the difference in the functioning of the HMGB1 and HMGB2 as well as their protein partners.

Acridine/Acridone-Carborane Conjugates as Strong DNA-Binding Agents with Anticancer Potential.

Synthesis of acridine derivatives that act as DNA-targeting anticancer agents is an evolving field and has resulted in the introduction of several drugs into clinical trials. Carboranes can be of importance in designing biologically active compounds due to their specific properties. Therefore, a series of novel acridine analogs modified with carborane clusters were synthesized. The DNA-binding ability of these analogs was evaluated on calf thymus DNA (ct-DNA). Results of these analyses showed that 9-[(1,7-dicarba-closo-dodecaborane-1-yl)propylamino]acridine (30) interacted strongly with ct-DNA, indicating its ability to intercalate into DNA, whereas 9-[(1,7-dicarba-closo-dodecaborane-1-yl)propanamido]acridine (29) changed the B-form of ct-DNA to the Z form. Compound 30 demonstrated cytotoxicity, was able to inhibit cell proliferation, arrest the cell cycle in the S phase in the HeLa cancer cell line, and induced the production of reactive oxygen species (ROS). In addition, it was specifically localized in lysosomes and was a weak inhibitor of Topo IIα.

Novel genosensor for probing DNA mismatches and UV-induced DNA damage: Sequence-specific recognition

Human genome is continuously susceptible to changes that may lead to undesirable mutations causing various diseases and cancer. Vast majority of techniques has investigated the discrimination between base-pair mismatched nucleic acid, but many of these techniques are time-consuming, complex, expensive, and limited to the detection of specific type of dsDNA mismatches. In this study, we introduce a simple mix-and-read assay for the sensitive and cost-effective analysis of DNA base mismatches and UV-induced DNA damage using Hoechst genosensor dye (H258). This dye is a minor groove binder that undergoes a drastic conformational change upon binding with mismatch DNA. The difference in binding affinity between perfectly matched and mismatched DNA was studied for sequences at different base mismatch locations and finally, extended for the detection of dsDNA damage by UVC radiation in calf thymus DNA. In addition, a comparative DNA damage kinetic study was performed using H258 (minor groove binder) and EvaGreen (intercalating) dye to get insight on assay selectivity and sensitivity with dye binding mechanism. The result shows good reproducibility making H258 genosensor a cheaper alternative for DNA mismatch and damage studies with possibility of extension for in-vitro detection of hot spots of DNA mutations.

Crystal structure, fluorescence properties, and biological activity of three Butterfly-shaped Ln4 compounds

Three tetranuclear lantharide-based compounds: [Ln4(dbm)4(L)6(μ3-OH)2]·CH3CN (LnIII = Eu (1), Tb (2) and Ho (3), HL = 5-(4-methylbenzylidene-8- hydroxyquinoline, dbm- = dibenzoylmethane) were fabricated and structurally characterized. X-ray diffraction studies reveal that all the compounds 1–3 belong to monoclinic crystal system with space group P21/n, and compounds 1–3 are isostructural and possess a rhombic Ln2O2 core. The solid-state luminescence property measurements indicated that the compounds 1 and 2 displayed the characteristic lanthanide luminescence at room temperature. Furthermore, biological activity researches revealed that the compounds 1–3 had better antibacterial activity against Escherichia coli, Bacillus subtilis, Staphylococcus aureus and Candida albicans than the ligand HL and Ln(dbm)3·2H2O (Ln = Eu, Tb, and Ho). The interaction between compounds 1–3 and calf thymus DNA was studied and the results revealed that the compounds were mainly intercalated with calf thymus DNA.

Effect of Severe Renal Dysfunction on the Plasma Levels of DNA-Reactive Platinum after Oxaliplatin Administration.

Higher amounts of circulating ultrafilterable platinum (fPt) are found in patients with renal dysfunction receiving a constant dose of oxaliplatin. However, the increased systemic fPt levels do not increase oxaliplatin-induced toxicities. We hypothesized that renal dysfunction has minimal effect on the elimination rate of reactive fPt, and that the DNA-binding capacity is one of the properties of reactive Pt species. This study aimed to quantify DNA-reactive fPt in plasma and to evaluate the impact of severe renal dysfunction on its pharmacokinetics. The pharmacokinetics of oxaliplatin was assessed in rats with bilateral nephrectomy (BNx) and in a hemodialysis patient who received mFOLFOX7 therapy for advanced metastatic gastric cancer. The platinum concentrations were determined using inductively coupled plasma-mass spectrometry. The amount of DNA-reactive fPt in the plasma was evaluated by the reaction between plasma and calf thymus DNA. Compared to the sham group in rats, the BNx group had significantly higher plasma total fPt concentrations at 24 h after drug administration. However, there was no significant difference in the plasma levels of DNA-reactive fPt between the two groups. In a hemodialysis patient, the plasma levels of total fPt decreased to 35.9 and 7.3% at 2 and 14 d after treatment, respectively. The plasma level of DNA-reactive fPt also decreased to 1.9 and 0.6%, respectively, on these days. This study showed that severe renal dysfunction has a limited effect on the plasma levels of DNA-reactive fPt after oxaliplatin administration.

Carboranyl-1,8-naphthalimide intercalators induce lysosomal membrane permeabilization and ferroptosis in cancer cell lines

The synthesis of carborane-1,8-naphthalimide conjugates and evaluation of their DNA-binding ability and anticancer activity were performed. A series of 4-carboranyl-3-nitro-1,8-naphthalimide derivatives, mitonafide and pinafide analogs, were synthesised via amidation and reductive amination reactions, and their calf thymus DNA (ct-DNA)-binding properties were investigated using circular dichroism, UV–vis spectroscopy, and thermal denaturation. Results showed that conjugates 34–37 interacted very strongly with ct-DNA (ΔT m = 10.00–13.00 °C), indicating their ability to intercalate with DNA, but did not inhibit the activity of topoisomerase II. The conjugates inhibited the cell growth of the HepG2 cancer cell line in vitro. The same compounds caused the G2M phase arrest. Cell lines treated with these conjugates showed an increase in reactive oxygen species, glutathione, and Fe2+ levels, lipid peroxidation, and mitochondrial membrane potential relative to controls, indicating the involvement of ferroptosis. Furthermore, these conjugates caused lysosomal membrane permeabilization in HepG2 cells but not in MRC-5 cells.