DNA Binding Studies Research Articles

AIEE activated Pyrene-Dansyl coupled FRET probe for discriminating detection of lethal Cu2+ and CN–: Bio-Imaging, DNA binding studies and prompt prognosis of Menke’s disease

In present work a pyrene-dansyl dyad functionalized chemoreceptor, DPNS is unveiled towards ultrasensitive chromo-fluorogenic detection of heavy and transition metal ions (HTMs) like Cu2+ and pernicious CN–. It demonstrated distinct chromogenic responses; colorless to faint yellow (Cu2+), intense yellow (CN–) from contaminant aqueous sources. Cu2+ instigated alteration in DPNS fluorescence from feeble emission to sparkling green with LOD: 37.75 × 10-9 M, cyan emission for CN– having LOD 61.51 × 10-8M. In particular, chemical scaffold of DPNS consists of –C = N, O = S = O donor entitities that escalates overall polarity thereby providing an excellent binding pocket for simultaneous Cu2+ and CN– recognition with distinct photophysical signaling. Impressively, presence of two fluorophoric moieties triggers FRET, CHEF phenomenon. The conceivable host:guest interactive pathway is manifested by LMCT- FRET-PET-CHEF, C = N isomerization for Cu2+ and ICT-H-bonding for CN–. An exquisite experimental and theoretical corroboration further strengthened the recognition phenomenon. In addition owing to pyrene excimer formation, DPNS exhibits AIEE with increasing water fraction. Notably, DPNS could successfully undergo intracellular tracking of Cu2+ in Tecoma Stans, Peperomia Pellucida. DPNS•••Cu2+ adduct displayed significant intercalative DNA binding activity rationalized by spectral investigation, competitive EB binding, viscosity study. The overall findings, excellent properties endows DPNS a potential contender towards discriminative detection of Cu2+ and CN– like toxic industrial contaminants.

Functional copper complexes with benzofurans tridentate ligand: Synthesis, crystal structure, DNA binding and anticancer studies

Metal complexes, particularly copper(II) complexes, are often used as anticancer drugs due to their ability to generate reactive oxygen species (ROS) in cells. Four copper(II) complexes have been designed based on ligands for triplet pyridine derivatives (complexes 1–4), and their structures have been determined using X-ray single crystal analysis. The interactions of these complexes with calf thymus DNA (CT-DNA) have been investigated using various techniques, including UV–vis absorption, viscosity measurements, and circular dichroism spectroscopy. The results indicate that complexes 1–4 strongly interact with DNA through partial intercalations. Further investigation using agarose gel electrophoresis shows that all four complexes can cleave pBR322 DNA in the presence of ascorbic acid as a reducing agent, and the DNA cleavage mechanism is through the generation of singlet oxygen (1O2). In vitro anticancer activities of these complexes have been evaluated using A549, MDA-MB-231, HeLa, and HepG2 cells. The calculated IC50 values indicate significant efficacy against cancer cells. Additionally, AO/EB staining assays reveal that these complexes induce cell apoptosis in HeLa cell line.

Low-dimensional compounds containing bioactive ligands. XXII. First crystal structure, cytotoxic activity and DNA and HSA binding of a zirconium(IV) complex with 8-hydroxyquinoline-2-carboxylic acid.

A new zirconium(IV) complex, diaquabis(8-hydroxyquinoline-2-carboxylato-κ3N,O2,O8)zirconium(IV) dimethylformamide disolvate, [Zr(C10H5NO3)2(H2O)2]·2C3H7NO or [Zr(QCa)2(H2O)2]·2DMF (1) (HQCaH is 8-hydroxyquinoline-2-carboxylic acid and DMF is dimethylformamide), was prepared and characterized by elemental analysis, IR spectroscopy and single-crystal X-ray structure analysis. Complex 1 is a mononuclear complex in which the ZrIV atoms sit on the twofold axis and they are octacoordinated by two N and six O atoms of two tridentate anionic QCa2- ligands, and two aqua ligands. Outside the coordination sphere are two DMF molecules bound to the complex unit by hydrogen bonds. The structure and stability of complex 1 in dimethyl sulfoxide were verified by NMR spectroscopy. The cytotoxic properties of 1 and HQCaH were studied in vitro against eight cancer cell lines, and their selectivity was tested on the BJ-5ta noncancerous cell line. Both the complex and HQCaH exhibited low activity, with IC50 > 200 µM. DNA and human serum albumin (HSA) binding studies showed that 1 binds to calf thymus (CT) DNA via intercalation and is able to bind to the tryptophan binding site of HSA (Trp-214).

A comparative study of novel ruthenium(III) and iron(III) complexes containing uracil; docking and biological studies

Structural and biological studies were conducted on the novel complexes [Fe(U)2(H2O)2]Cl3 (FeU) and [Ru(U)2(H2O)2]Cl3 (RuU) (U = 5,6-Diamino-1,3-dimethylpyrimidine-2,4(1H,3H)-dione) to develop an anticancer drug candidate. The two complexes have been synthesized and characterized. Based on our findings, these complexes have octahedral geometry. The DNA-binding study proved that both complexes coordinated with CT-DNA. The docking study confirmed the potency of both complexes in downregulating the topoisomerase I protein through their high binding affinity. Biological studies have established that both complexes can act as potent anticancer agents against three cancer cell lines. RuU or FeU complexes induce apoptosis in breast cancer cells by increasing caspase9 protein and inhibiting proliferating cell nuclear antigen (PCNA) activity. In addition, both complexes down-regulate topoisomerase I expression in breast cancer cells. Therefore, the RuU and FeU complexes' anticancer activities were mediated via both apoptosis induction and topoisomerase I down-regulation. In conclusion, both complexes have dual anticancer activity pathways that may be responsible for the selective cytotoxicity of the complexes. This makes them more suitable for the development of novel cancer treatment strategies.

Comparative DNA-/BSA-binding, DNA cleavage, and cytotoxic properties of copper(II) amino/salicyl-phenolate Schiff bases (phen) complexes that induce generation of phenoxyl radicals

A series of mixed-ligand Cu(II) complexes of the type [Cu(L1-5)(diimine)(H2O)](ClO4) (1–5) and [Cu(L6)(diimine)](ClO4) (6), where HL1-HL4 are aminophenolate Schiff base ligands viz., 2-(benzylideneamino)phenol (HL1, 1), 2-(4-fluorobenzylideneamino)phenol (HL2, 2), 2-(4-chlorobenzylideneamino)phenol (HL3, 3), and 2-(4-nitrobenzylideneamino)phenol (HL4, 4) whereas HL4 and HL5 are salicyl-phenolate Schiff base ligands viz.,2-((phenylimino)methyl)phenol (HL5, 5) and (E)-2-(((2-(dimethylamino)ethyl)imino)methyl)phenol (HL6, 6) as primary ligands and the diimine 1,10-phenanthroline (phen) as co-ligand have been isolated. TheSchiffbaseligandsand their mixedligandchelates were characterizedby spectral techniques (UV–Visible, IR, mass, 1H, and 13C NMR), elemental analysis, cyclic voltammetry (CV), and differential pulse voltammetric (DPV) techniques. The molecular structure of 6, which alone formed appreciable crystals, was determined by single-crystal X-ray studies, and two crystallographically independent molecules (a and b) existed in square pyramidal distorted trigonal bipyramidal (SPDTBP) geometry. The complexes 1–4 showed a reversible (ΔEp for 3; 64), quasi-reversible (2; 105 and 4; 115), and irreversible (1; 181 mV) oxidation waves discernible at E1/2 ranging from + 0.035 V to −0.120 V (DPV) which are attributed to the formation of copper(II)-phenoxyl radical species. Among them, 2 and 3 showed a well-defined reversible phenoxyl radical formation in CV and DPV. Also, these two complexes exhibited more stable phenoxyl radical in the presence of CAN (cerium ammonium nitrate). The DNA binding studies revealed that the fluoro- and chloro-substituted complexes 2 and 3 exhibited higher DNA binding propensity than the other complexes. All the complexes displayed moderate to high oxidative DNA cleavage property in the presence of H2O2, wherein complexes 2 and 3 exhibited higher DNA cleavage than the others. Interestingly, complex 3 exhibited less AC50 value (18.26 µM) than complex 2 (43.3 µM). The mechanistic study led to the inference that the DNA cleavage is possibly mediated via copper(II)-bound phenoxyl-radical. The cytotoxicity of complexes 1–6 was investigated in A549 non-small cell lung carcinoma cell. The amino-phenolate complexes 2 (IC50 = 3.52 µM) and 3 (IC50 = 3.4 µM) brought about higher cytotoxicity and ≈ 3.8-times more potency than cisplatin. The complex 3 showed to be 47-times less toxic to non-cancerous peripheral blood mononuclear cells (PBMC). Fluorescent staining assay revealed that the complexes 1–6 induced apoptotic cell death with some degree of necrosis. JC-1 staining assay revealed that complex 3 efficiently depolarized the mitochondrial membrane potential. Put together, the results substantiate that amino-phenolate-containing copper(II) mixed ligand complexes are more cytotoxic than salicyl-phenolate-containing copper(II) complexes.

Computational studies, cytotoxicity, DNA interactions of bioactive novel 2-methoxy 5-trifluoromethyl benzenamine Schiff base metal complexes

Two novel Schiff base ligands (HL1), (HL2) and their metal(II) complexes [Co(HL1)2(H2O)2]-A; [Ni(HL1)2]-B; [Cu(HL1)2]-C; [Co(HL2)2(H2O)2]-D; [Ni(HL2)2]-E; [Cu(HL2)2]-F have been characterized by various techniques (NMR, FTIR, ESI mass, UV-Visible, ESR, TGA) and confirmed that Ni (II), Cu(II) complexes exhibit square planar geometry whereas Co(II) complexes exhibit octahedral geometry. Interaction experiments involving DNA binding and cleavage studies have revealed that the mode of binding is intercalative and complexes effectively cleave supercoiled DNA. Pathological tests of all compounds against microbial strains in vitro showed that all complexes are more potent than free ligands and Cu(II) complexes are more potent than other complexes. Higher antioxidant activity (by DPPH method) was found by Cu(II) complexes. In addition, synthesized compounds were evaluated for their in-vitro cytotoxic potential against human breast cancer cell (MCF-7) and oral cancer cell (KB3) using cis-platin as a standard drug by MTT assay and found complexes are more potent than free ligands.

Chemical Synthesis, Characterization and DNA Binding Studies of 2, 4- Dihydroxy Acetophenone Pramipexole Schiff Base Metal Complexes

Schiff and their complexes are versatile compounds synthesized from the condensation of an amino compound with carbonyl compounds and widely used for industrial purposes and also exhibit a broad range of biological activities, including antifungal, antibacterial, anti-malarial, ant proliferative, anti-inflammatory, antiviral, and antipyretic properties. Many Schiff base complexes show excellent activity in various reactions in the presence of moisture. Over the past few years, many reports have been on their applications in homogeneous and heterogeneous catalysis. The influence of certain metals on the biological activity of these compounds and their intrinsic chemical interest as multidentate ligands has prompted a considerable increase in the study of their coordination behavior. The development of new chemotherapeutic Schiff bases and their metal complexes is now attracting the attention of medicinal chemists. The present paper deals with synthesizing and characterizing metal complexes of new Schiff bases derived from Pramipexole (4, 5, 6, 7-Tetrahydro-N6-propyl-2, 6-benzothiazole diamine) and 2,4- dihydroxy acetophenone (2,4 DHAP) by using modified Sand Mayer's method. Synthesized complexes were characterized by several techniques using IR, 1HNMR, UV-visible spectrometry, TG-DTA, and Conduct Metric Titrations. Infrared spectral data indicate the coordination between ligand and central metal ion through deprotonated phenolic oxygen and azomethine nitrogen. In addition, the authors have screened the compounds for DNA binding studies. It was found that these complexes bind DNA with high affinities.

Transcriptional activation of ompA in Neisseria gonorrhoeae mediated by the XRE family member protein NceR.

Increasing antibiotic resistance of Neisseria gonorrhoeae, the causative agent of gonorrhea, is a growing global concern that has renewed vaccine development efforts. The gonococcal OmpA protein was previously identified as a vaccine candidate due to its surface exposure, conservation, stable expression, and involvement in host-cell interactions. We previously demonstrated that the transcription of ompA can be activated by the MisR/MisS two-component system. Interestingly, earlier work suggested that the availability of free iron also influences ompA expression, which we confirmed in this study. In the present study, we found that iron regulation of ompA was independent of MisR and searched for additional regulators. A DNA pull-down assay with the ompA promoter from gonococcal lysates obtained from bacteria grown in the presence or absence of iron identified an XRE (Xenobiotic Response Element) family member protein encoded by NGO1982. We found that an NGO1982 null mutant of N. gonorrhoeae strain FA19 displayed a reduced level of ompA expression compared to the wild-type (WT) parent strain. Given this regulation, and the capacity of this XRE-like protein to regulate a gene involved in peptidoglycan biosynthesis (ltgA), along with its presence in other Neisseria sp., we termed the NGO1982-encoded protein as NceR (Neisseria cell envelope regulator). Critically, results from DNA-binding studies indicated that NceR regulates ompA through a direct mechanism. Thus, ompA expression is subject to both iron-dependent (NceR) and -independent (MisR/MisS) pathways. Hence, levels of the vaccine antigen candidate OmpA in circulating gonococcal strains could be influenced by transcriptional regulatory systems and the availability of iron. IMPORTANCE Herein, we report that the gene encoding a conserved gonococcal surface-exposed vaccine candidate (OmpA) is activated by a heretofore undescribed XRE family transcription factor, which we term NceR. We report that NceR regulation of ompA expression in N. gonorrhoeae is mediated by an iron-dependent mechanism, while the previously described MisR regulatory system is iron-independent. Our study highlights the importance of defining the complexity of coordinated genetic and physiologic systems that regulate genes encoding vaccine candidates to better understand their availability during infection.

Synthesis, physicochemical characterisation and DNA binding study of a novel azo Schiff base Ni(II) complex

The azo Schiff base ligand was synthesised, along with its Ni(II) complex, by diazotisation of salicylaldehyde with 4-nitroaniline in accordance with the accepted literature approach. Using a variety of spectroscopic techniques, the resulting complex is analysed both quantitatively and qualitatively (Elemental analysis, FT-IR spectroscopy, UV-VIS spectroscopy, 1H NMR, etc.). Spectral measurements of the complex revealed a mole ratio of 1:1. The non-electrolytic nature of the complex is confirmed by molar conductance investigation. The unique azo compound had a tetrahedral shape as a result of the tetra coordination of two phenolic oxygen and two imine nitrogen. The ability of the metal complexes to bind DNA was examined using absorption spectroscopy, fluorescence spectroscopy, viscosity tests, and thermal denaturation methods. Experimental research suggests that complexes bind to DNA through intercalation.

Electro-organic synthesis of C-5 sulfenylated amino uracils: Optimization and exploring topoisomerase-I based anti-cancer profile

Cancer is spreading worldwide and is one of the leading causes of death. The use of existing chemotherapeutic agents is frequently limited due to side effects. As a result, it is critical to investigate new agents for cancer treatment. In this context, we developed an electrochemical method for the synthesis of a series of thiol-linked pyrimidine derivatives (3a-3p) and explored their anti-cancer potential. The biological profile of the synthesized compounds was evaluated against breast (MDAMB-231 and MCF-7) and colorectal (HCT-116) cancer cell lines. 3b and 3d emerged to be the most potent agents, with IC50 values ranging between 0.98 to 2.45 µM. Target delineation studies followed by secondary anticancer parameters were evaluated for most potent compounds, 3b and 3d. The analysis revealed compounds possess DNA intercalation potential and selective inhibition towards human topoisomerase (hTopo1). The analysis was further corroborated by DNA binding studies and in silico-based molecular modeling studies that validated the intercalating binding mode between the compounds and the DNA.

Glycine methyl ester based Schiff base bearing long alkoxy arm and its zinc(II) and copper(II) complexes: Synthesis, mesomorphism, photoluminescence, CT-DNA interaction and DFT study

A new photoluminescent mesogenic glycine methyl ester based Schiff base ligand and its zinc(II) and copper(II) complexes have been synthesised. The compounds were characterized by elemental analyses, Fourier transform infrared spectroscopy (FT-IR), 1H, 13C nuclear magnetic resonance (NMR), ultraviolet–visible spectroscopy (UV–Vis), ESI-MS, MALDI-TOF, EDX and thermogravimetric analysis (TGA). The polarizing optical microscopy (POM) and differential scanning calorimetry (DSC) study revealed that the ligand and zinc(II) complex possess SmecticA mesophase on heating but copper(II) complex is non-mesogenic. The optical absorption and fluorescence spectroscopy studies of zinc(II) complex indicate the existence of aggregation/ de-aggregation species in the presence of non-coordinating and coordinating solvents. The Density Functional Theory (DFT) study was carried out using LanL2DZ and 6–31 G (d, p) basis set with meta-hybrid Truhlar's functional M06–2X to obtain a stable, optimized structure, HOMO-LUMO energy gap and chemical hardness. As designed, the combination of both the –CN- and -COO- linkages plays significant role to influence the mesomorphic behaviour as well as biogenic properties of the compounds. The in vitro interactions of the compounds with CT-DNA has been investigated using UV–Vis and fluorescence spectroscopy. To the best of our knowledge, this is one of the few report on DNA binding studies of mesogenic amino acid Schiff base, which is having binding constant in the same range with the gold standard compound, ethidium bromide.

Sequence-Specific Dual DNA Binding Modes and Cytotoxicities of N-6-Functionalized Norcryptotackieine Alkaloids.

Norcryptotackieine (1a) belongs to the indoloquinoline class of alkaloids isolated from Cryptolepis sanguinolenta, a plant species that has been traditionally used as an antimalarial agent. Additional structural modifications of 1a can potentially enhance its therapeutic potency. Indoloquinolines such as cryptolepine, neocryptolepine, isocryptolepine, and neoisocryptolepine show restricted clinical applications owing to their cytotoxicity deriving from interactions with DNA. Here, we examined the effect of substitutions at the N-6 position of norcryptotackieine on the cytotoxicity, as well as structure-activity relationship studies pertaining to sequence specific DNA-binding affinities. The representative compound 6d binds DNA in a nonintercalative/pseudointercalative fashion, in addition to nonspecific stacking on DNA, in a sequence selective manner. The DNA-binding studies clearly establish the mechanism of DNA binding by N-6-substituted norcryptotackieines and neocryptolepine. The synthesized norcryptotackieines 6c,d and known indoloquinolines were screened on different cell lines (HEK293, OVCAR3, SKOV3, B16F10, and HeLa) to assess their cytotoxicity. Norcryptotackieine 6d (IC50 value of 3.1 μM) showed 2-fold less potency when compared to the natural indoloquinoline cryptolepine 1c (IC50 value of 1.64 μM) in OVCAR3 (ovarian adenocarcinoma) cell lines.

Synthesis, characterization, X‐ray structure, DNA binding, antioxidant and docking study of new organotin(IV) complexes

Four new diorganotin(IV) complexes, including Me2SnL(1), Bu2SnL(2), Ph2SnL(3) and Oct2SnL(4), were synthesized by reacting R2SnCl2 (where R = Me, Bu, Ph, Oct) with N′‐(3,5‐dichloro‐2‐hydroxybenzylidene)‐2‐phenylacetohydrazide H2L. The synthesized ligand and complexes were structurally characterized by various techniques, including Fourier transform infrared (FT‐IR), 1H and 13C nuclear magnetic resonance (NMR) and mass spectrometry. The data suggested that tin–oxygen and tin–nitrogen bonds are formed during complex formation, confirming the coordination of ligand with dialkyltin(IV) moieties and the presence of penta‐coordinated structures. The single‐crystal X‐ray study was performed to confirm the molecular structure of complex 1, which revealed that the molecular structure is distorted towards square pyramidal geometry. The compound–DNA interaction was investigated via spectroscopic, electrochemical and molecular docking studies; the mode of interaction found in all cases was intercalative in nature. The complex 3 showed the highest binding ability with sodium salt of salmon sperm DNA (SS‐DNA) (1.93 × 105 M−1). The data obtained for DNA interaction studies from theoretical calculation via docking studies match well with those observed from spectroscopic and electrochemical analyses. Electrochemical and thermodynamic parameters, including diffusion coefficient, ∆H, ∆G and ∆S, were also calculated. The DPPH antioxidant results showed that complex 2 is an active antioxidant.

Synthesis, single crystal, TD-DFT, molecular dynamics simulation and DNA binding studies of carbothioamide analog

In this work, analog 3b (5-(4-(dimethylamino) phenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide) of pyrazoline derivative was produced based on the active site (CYP51) analysis. To elucidate its molecular structure, various techniques including FT-IR, UV–visible, NMR, mass spectrometry and X-ray crystallography were utilised. The bond lengths and bond angles occur in monoclinic with P21/n space group for 3b, and z = 8 corresponds to compound 3b, and the lattice parameters show, a = 14.5480(14) Å, b = 17.0119(17) Å, c = 14.6257(14) Å, α = 90˚, β = 98.646(3)˚, γ = 90˚ per unit cell. Analog 3b also showed significant antifungal activity against candida strains, C. albicans, C. glabrata, and C. tropicalis and molecular docking performed at the active site of 14-alpha demethylase, and an estimated ADME assay was calculated. In addition, simulation of the CYP51 protein-ligand complexes at a time scale of 100 ns showed that the mean RMSD is 0.31 nm. According to the simulation and MMGBSA data, protein-ligand complexes are stable and exhibit stable interactions up to 100 ns of simulation time. The DNA binding was revealed by using UV–vis, fluorescence and cyclic voltammetry measurements. TD-DFT calculation was used to study several computational structural characteristics of molecule. We also used Hirshfeld surface analysis (HSA), FTIR, UV–Vis. and NMR spectra to compare the structural features of theoretical and experimental findings of the molecule 3b. The comprehensive in-silico and experimental study confirm the synthesised pyrazoline analog's antifungal, antioxidant, and DNA binding properties.

Structural characterization, DNA binding study, antioxidant potential and antitumor activity of diorganotin(IV) complexes against human breast cancer cell line MDA-MB-231

Five new organotin(IV) complexes, Me2SnL (1), Bu2SnL (2), t-Bu2SnL (3), Ph2SnL (4) and Oct2SnL (5), have been synthesized from the reaction of R2SnCl2 (R= Me, Bu, tert-Bu, Ph, Oct) with N'-(3-ethoxy-2-hydroxybenzylidene)formohydrazide (H2L). The structural elucidation of synthesized compounds was done by FT-IR, 1H-NMR, 13C-NMR spectroscopy and single-crystal X-ray analysis. Crystallographic data of complex (1) showed seven coordinated central tin atom with distorted pentagonal bipyramidal geometry. Where in solution the Sn atom of synthesized complexes exhibit five coordination, confirmed from 1H-NMR. The results from DNA interaction studies via UV-visible spectroscopy, viscosity, cyclic voltammetry, and differential pulse voltammetry (DPV) suggested an intercalative mode of interaction between the synthesized compounds and SS-DNA. Furthermore, the complexes interact more significantly than ligand. Electrochemical and thermodynamic parameters, including diffusion coefficient, ∆H, ∆G, and ∆S, were calculated using cyclic voltammetry data. The linear plot of peak current (I) vs. square root of the scan rate (υ1/2) indicated the electrochemical processes to be diffusion controlled. The DPPH free radical scavenging assay results showed that complex (4) is an active antioxidant. In-vitro cytotoxicity of the synthesized compounds was determined on human breast cancer cell line MDA-MB-231 using tetrazolium-based MTT assay, and complexes (2), (3) and (4) showed significant cytotoxic activity. The structure-activity relationships may be utilised to direct the optimization of the activity of agents from this class of compounds by comparing the specifics of the compound structures, their DNA binding, and toxicity.

High Intrinsic Oncogenic Potential in the Myc-Box-Deficient Hydra Myc3 Protein.

The proto-oncogene myc has been intensively studied primarily in vertebrate cell culture systems. Myc transcription factors control fundamental cellular processes such as cell proliferation, cell cycle control and stem cell maintenance. Myc interacts with the Max protein and Myc/Max heterodimers regulate thousands of target genes. The genome of the freshwater polyp Hydra encodes four myc genes (myc1-4). Previous structural and biochemical characterization showed that the Hydra Myc1 and Myc2 proteins share high similarities with vertebrate c-Myc, and their expression patterns suggested a function in adult stem cell maintenance. In contrast, an additional Hydra Myc protein termed Myc3 is highly divergent, lacking the common N-terminal domain and all conserved Myc-boxes. Single cell transcriptome analysis revealed that the myc3 gene is expressed in a distinct population of interstitial precursor cells committed to nerve- and gland-cell differentiation, where the Myc3 protein may counteract the stemness actions of Myc1 and Myc2 and thereby allow the implementation of a differentiation program. In vitro DNA binding studies showed that Myc3 dimerizes with Hydra Max, and this dimer efficiently binds to DNA containing the canonical Myc consensus motif (E-box). In vivo cell transformation assays in avian fibroblast cultures further revealed an unexpected high potential for oncogenic transformation in the conserved Myc3 C-terminus, as compared to Hydra Myc2 or Myc1. Structure modeling of the Myc3 protein predicted conserved amino acid residues in its bHLH-LZ domain engaged in Myc3/Max dimerization. Mutating these amino acid residues in the human c-Myc (MYC) sequence resulted in a significant decrease in its cell transformation potential. We discuss our findings in the context of oncogenic transformation and cell differentiation, both relevant for human cancer, where Myc represents a major driver.

Covalent synthesis, structural characterization and biological behavioral study of tin captured porphyrin-polyoxometalate based polymeric hybrid

The combination of polyoxometalates(POMs) and tin-based porphyrin in a variety of modes ofinteractionturned out to be the key for unlocking new directions in the study of biological activities. In this study, a new sandwich type covalently attached porphyrin C52H48N6O6Sn (SnTPP-Di-Tris) and Anderson POM-porphyrin polymeric hybrid, with molecular formula as [{N(C4H9)4}8{C62H60Mn2Mo12N6O48Sn·CH3CN}](PolySnP@POM). These compounds were clearly characterized and their formation was confirmed by spectroscopic (UV–visible, FT-IR, NMR) techniques, powder XRD, elemental analyses, cyclic voltammetry and scanning electron microscopy techniques(SEM). SnTPP-Di-Tris and PolySnP@POM were evaluated for drug delivery, DNA binding, protein binding and antibacterial studies. It is found that drug loading efficiency was 89% and 93% for PolySnP@POM and SnTPP-Di-Tris, respectively. While drug release was more efficient in acidic media (pH = 3) as 100 % for both compounds in 1.5 h as compared to basic media (pH = 11) 65.93% and 72.6% for SnTPP-Di-Tris and PolySnP@POM, respectively. Uv–visible study of SnTPP-Di-Tris and PolySnP@POM with salmon sperm DNA (SS-DNA) showed hypochromism trend which indicate intercalation mode of attachment and exhibited binding constant value 4.9 × 103 M−1 and 2.7 × 104 M−1 for SnTPP-Di-Tris and PolySnP@POM, respectively, referring that PolySnP@POM has more binding affinity than SnTPP-Di-Tris. Protein binding Study presented binding constant value (Kb) 3.09 × 104 M−1 and 1.30 × 104 M−1 for PolySnP@POM, and SnTPP-Di-Tris, correspondingly. Antibacterial activity results showed minor to significant activity. Furthermore, enhanced antibacterial activity of SnTPP-Di-Tris over its corresponding hybrid PolySnP@POM was observed because of lipophilic and more proliferating nature of SnTPP-Di-Tris.

Steric hindrance, ligand ejection and associated photocytotoxic properties of ruthenium(II) polypyridyl complexes

Two ruthenium(II) polypyridyl complexes were prepared with the {Ru(phen)2}2+ moiety and a third sterically non-hindering bidentate ligand, namely 2,2′-dipyridylamine (dpa) and N-benzyl-2,2′-dipyridylamine (Bndpa). Hence, complexes [Ru(phen)2(dpa)](PF6)2 (1) and [Ru(phen)2(Bndpa)](PF6)2 (2) were characterized and their photochemical behaviour in solution (acetonitrile and water) was subsequently investigated. Compounds 1 and 2, which do not exhibit notably distorted octahedral coordination environments, contrarily to the homoleptic “parent” compound [Ru(phen)3](PF6)2, experience two-step photoejection of the dpa and Bndpa ligand upon irradiation (1050–430 nm) for several hours. DNA-binding studies revealed that compounds 1 and 2 affect the biomolecule differently upon irradiation; while 2 solely modifies its electrophoretic mobility, complex 1 is also capable of cleaving it. In vitro cytotoxicity studies with two cancer-cell lines, namely A549 (lung adenocarcinoma) and A375 (melanoma), showed that both 1 and 2 are not toxic in the dark, while only 1 is significantly cytotoxic if irradiated, 2 remaining non-toxic under these conditions.Graphical abstractLight irradiation of the complex cation [Ru(phen)2(dpa)]2+ leads to the generation of transient Ru species that is present in the solution medium for several hours, and that is significantly cytotoxic, ultimately producing non-toxic free dpa and [Ru(phen)(OH2)2]2+.

Synthesis of water-soluble novel bioactive pyridine-based azo coumarin derivative and competitive cytotoxicity, DNA binding, BSA binding study, and in silico analysis with coumarin

The diazo coupliling reaction of 3- amino pyridine with coumarin in water medium produces water soluble 6-[3-pyridyl]azocoumarin. The synthesised compound has been fully charecterised by IR, NMR, and Mass spectroscopy. The frontier molecular orbital calculations reveal that 6-[3-pyridyl]azocoumarin is more biologically and chemically active in comparison to coumarin. The cytotoxicity evaluation confirms that 6-[3-pyridyl]azocoumarin is more active than coumarin against human brain glioblastoma cell lines, LN-229 with IC50 value 9.09 μM (IC50 value for coumarin is 9.9 μM). The compound (I) has been synthesized by coupling of diazotized solution of 3-aminopyridine with coumarin in an aqueous medium at ∼ pH 10. The structure of the compound (I) has been characterized using UV–vis, IR, NMR, and Mass spectral studies. Frontier molecular orbital calculations reveal that 6-[3-pyridyl]azocoumarin (I) is more active chemically and biologically in comparison to coumarin. IC50 value 9.09 and 9.9 μM of 6-[3-pyridyl]azocoumarin and coumarin respectively obtained in cytotoxicity evaluation confirms the enhanced activity of the synthesized compound against human brain glioblastoma cell lines, LN-229. The synthesized compound also shows strong binding interactions with DNA and BSA in comparison with coumarin. The DNA binding study shows groove binding interaction of the synthesized compound with CT-DNA. The nature of interaction, binding parameters and structural variations of BSA in the presence of the synthesized compound and coumarin have been evaluated using several usefull spectroscopy approaches such as UV –Vis, time resolved and stady state flurescence. The molecular docking interaction has been carried out to justify the experimental binding interaction with DNA and BSA.

Preparation and spectroscopic properties of bioactive 1, 2, 3-triazole-linked boronate esters for use in antioxidant, antimicrobial, and DNA binding studies

In this article, the preparation, spectral evaluation, and biological studies of bioactive 1, 2, 3-triazole-linked boronate esters are reported. The bioactive 1, 2, 3-triazole group linked-boronate esters have been designed and obtained by azido-functionalized boronate ester with different alkyne molecules via click chemistry approach under mild conditions. The prepared boronate esters (B1-5) were characterized using NMR (1H, 13C, and 11B) spectra, FT-IR spectra, UV-Vis spectra, LC-MS/MS spectra, elemental analysis, and melting point measurement techniques. After all structures of synthesized boronate esters were characterized in detail, the antimicrobial (antioxidant and antibacterial) and DNA binding properties of newly prepared boronate esters were investigated. The bioactive 1, 2, 3-triazole-linked boronate ester (B5) showed the highest radical scavenging (71.59 ± 1.85%) and reducing power activity (0.476 ± 0.01) at 200.0 µg/mL concentration. According to the method of reducing power activity, the compound (B5) exhibited the strongest activity with 0.476 ± 0.014. The anti-bacterial activity of all boronate esters (B1-5) was determined with four pathogenic bacteria. It was determined that only the 1, 2, 3-triazole-linked boronate ester (B5) showed low activity against two bacteria (8 mm for S. aureus and 10 mm for E. hirae), while other boronate esters were found to have no activity. According to electrophoresis results using calf thymus DNA (CT-DNA), 1, 2, 3-triazole-linked boronate esters (B3-5) were determined to have DNA binding activity.