Groove Binding Interaction Research Articles

Diorganotin(IV) derivatives of salicylaldehyde hydrazones: Synthesis, structural characterization, crystal structure of dimethyltin(IV) complexes, and CT-DNA binding

Six new diorganotin(IV) complexes of H2L1 and H2L2 (Me2SnL1, n-Bu2SnL1, Ph2SnL1, Me2SnL2, n-Bu2SnL2, and Ph2SnL2) and six recently reported diorganotin(IV) complexes of H2L3 and H2L4 (Me2SnL3, n-Bu2SnL3, Ph2SnL3, Me2SnL4, n-Bu2SnL4, and Ph2SnL4) have been synthesized and characterized by CHN analyses, FT-IR, multinuclear NMR including 1H, 13C and 119Sn, ESI-MS and single crystal X-ray diffraction studies. Hydrazones (H2L1–4) are derived from the condensation of indole-2-acetic hydrazide and salicylaldehyde (H2L1)/4-methoxysalicylaldehyde (H2L2)/5-chlorosalicylaldehyde (H2L3)/5-bromosalicylaldehyde (H2L4). Single-crystal X-ray (Sc-X-ray) diffraction studies of Me2SnL1 (1) and Me2SnL4 (10) confirm the di-anionic and tridentate (ONO) behaviour of hydrazones, which may bind with organotin(IV) moiety via enolic oxygen, phenolic oxygen, and azomethine nitrogen. Further, Sc-X-ray diffraction studies suggested that the complexes have distorted square-pyramidal geometry. The groove binding or electrostatic interactions of H2L1–4 and R2SnL1–4 (1–12) with CT-DNA have been validated by investigating UV–Vis, fluorescence, and circular dichroism (CD) spectral titrations which revealed that H2L1–4 and R2SnL1–4 (1–12) have binding constants with CT-DNA in the range ∼105 M−1.

Synthesis, Characterization, DNA Binding, Biological Significance, and Molecular Docking Approaches of a Palladium(II) Complex with Ciprofloxacin for More Efficient Therapy.

To evaluate the biotransformation and the mechanism of binding as well as the biological impact of metal-based- drugs involving Pd(II), known to have high potency and low toxicity for use as anticancer therapeutics, in the present study, a newly synthesized palladium (II) complex, [Pd(CPF)(OH2)2]2+ (where CPF is ciprofloxacin), has been synthesized and characterized and thoroughly evaluated for its antimicrobial properties. The interaction of the diaqua complex with CT-DNA and BSA was studied through various techniques, including UV-vis spectroscopy, thermal denaturation, viscometry, gel electrophoresis, ethanol precipitation, and molecular docking studies. The results indicate that the complex exhibits a robust binding interaction with CT-DNA, possibly via minor groove binding and (or) electrostatic interactions. Furthermore, the complex displays good binding affinity towards BSA, indicating its potential as a target for DNA and BSA in biological media. The invitro cytotoxicity assay reveals that this complex can be classified as a promising cell growth inhibitor against MCF-7, HT-29, and A549. Thus, this newly synthesized palladium (II) complex is a promising candidate for further exploration as a potential anticancer therapeutic.

Experimental and molecular modelling demonstration of effective DNA and protein binding as well as anticancer potential of two mononuclear Cu(II) and Co(II) complexes with isothiocyanate and azide as anionic residues

In the present study, one mononuclear Cu(II) [CuL(SCN)] (1) and one mononuclear Co(II) [CoLN3] (2) complexes, with a Schiff base ligand (HL) formed by condensation of 2-picolylamine and salicylaldehyde, have been successfully developed and structurally characterized. The square planer geometry of both complexes is fulfilled by the coordination of one deprotonated ligand and one ancillary ligand SCN−(1) or N3−(2) to the metal centre. Binding affinities of both complexes with deoxyribonucleic acid (DNA) and human serum albumin (HSA) are investigated using several biophysical and spectroscopic techniques. High values of the macromolecule-complex binding constants and other results confirm the effectiveness of both complexes towards binding with DNA and HSA. The determined values of the thermodynamic parameters support spontaneous interactions of both complexes with HSA, while fluorescence displacement and DNA melting studies establish groove-binding interactions with DNA for both complexes 1 and 2. The molecular modelling study validates the experimental findings. Both complexes are subjected to an MTT test establishing the anticancer property of complex 1 with lower risk to normal cells, confirmed by the IC50 values of the complex for HeLa cancer cells and HEK normal cells. Finally, a nuclear staining analysis reveals that the complexes have caused apoptotic cell death.

Trimethyltin(IV) (p-fluoro-/p‑hydroxy-/p-nitro-)benzoates and their benzimidazole complexes: X-ray structures of [Me3Sn(p-NO2C6H4CO2)]n, and [Me3Sn(p-NO2C6H4CO2). bz], DFT calculations, DNA binding, and DNA cleavage studies

A series of trimethyltin(IV) carboxylates with Sn‒O bonds: [Me3Sn(p-FC6H4CO2)] (1), [Me3Sn(p-HOC6H4CO2)] (2), [Me3Sn(p-NO2C6H4CO2)]n (3), and their benzimidazole complexes with Sn‒N bond: [Me3Sn(p-FC6H4CO2).bz] (4), [Me3Sn(p-HOC6H4CO2).bz] (5), and [Me3Sn(p-NO2C6H4CO2).bz] (6) (bz = benzimidazole) have been synthesized and characterized by elemental analysis, FT-IR, 1H, 13C, 119Sn NMR, and electrospray ionization mass spectrometric (ESI-MS) studies. The crystal structures for (3) and (6) have been authenticated by X-ray diffraction. In the crystal structure, polymeric coordination compound (3) and the monocrystal system (6) have trigonal bipyramidal geometry around the Sn centre, where most electronegative atoms occupied the axial positions, and three methyl groups occupied the equatorial positions. The gas-phase tetrahedral geometries of (1) and (2), asymmetric unit (Sc-XRD) of (3), and trigonal bipyramidal geometries of (4–6) have been optimized using the B3LYP function and LanL2Z basis, and obtained ∠C-Sn-C bond angles agree with those obtained from NMR/X-ray studies. The interaction of (1–6) with calf thymus DNA (ctDNA) has been investigated by spectroscopic titrations such as UV–visible, fluorescence, and circular dichroism (CD) titrations, and calculated binding constant values found in the 104–105 M−1 range which suggest a groove binding or electrostatic interaction between complexes and ctDNA. The gel electrophoresis studies suggest that (1–6) effectively cleaved the plasmid pBR322 DNA into three bands: the supercoiled, nicked/circular, and linear structures. The intriguing biophysical findings from the study indicate that these complexes have properties that make them strong contenders for additional research as potential anti-cancer agents.

Ru(II)‐arene complexes with phenolic acid ligands: Synthesis, density function theoretical calculations, anti‐cancer studies, and cell death mechanisms

Six new complexes (1–6), [Ru(η6‐p‐cymene)(FA)Cl] (1), [Ru(η6‐p‐cymene)(PA)Cl] (2), [Ru(η6‐p‐cymene)(SA)Cl] (3), [Ru(η6‐p‐cymene)(FA)PPh3]Cl (4), [Ru(η6‐p‐cymene)(PA)PPh3]Cl (5), [Ru(η6‐p‐cymene)(SA)PPh3]Cl(6), [HFA = ferulic acid, HPA = p‐coumaric acid, HSA = sinapinic acid], were synthesized and well characterized by various spectroscopic, analytical techniques and computational studies. Amongst these six complexes, complexes 4, 5, and 6 were found to be selectively cytotoxic toward melanoma (A375) cell lines and were non‐cytotoxic toward non‐cancerous cell lines (HEK 293 T). Further investigation on the probable bio‐molecular interaction mechanisms revealed that all the complexes show strong groove binding interactions with the DNA, however, complexes 3, 4 and 3, 6 show strong interaction with BSA and HSA, respectively. Through Hoechst staining it can be elucidated that complexes 4–6 cause characteristic apoptotic nuclear changes in the cells indicating apoptosis as the cell death mechanism caused by complexes 4–6. To further confirm the cell death mechanism, protein expression analysis was done through western blotting, which showed a decrease in anti‐apoptotic protein (Bcl‐xL) expression and increased pro‐apoptotic protein (PARP) expression, which confirms the cell death by apoptosis. Using DCFDA staining, we observed that complexes 4, 5, and 6 produced more ROS in the cells, which also might be the cause of cell death by the complexes. Along with that the complexes show enhanced anti‐migratory abilities depicted through wound healing assay.

Biophysical profiling and in vitro study of apocarotenoids with calf thymus DNA to explore their efficacy in adjuvant cancer therapy

DNA is one of the important targets for therapeutic drugs. Investigating the interaction between these drug molecules and DNA yields valuable insights for the further advancement of medication formulations. In this study, we explore the interaction between calf thymus-DNA and temozolomide with apocarotenoids such as bixin and crocin, which are known for their therapeutic activities. The combinatory effect of the compounds on ct-DNA was studied through diverse spectroscopic methods including UV-visible, circular dichroism studies coupled with viscosity and cell cycle analysis. UV-visible spectroscopy evaluation indicates that apocarotenoids and the temozolomide combination display a non-intercalative binding mechanism. The circular dichroism study revealed that the interaction between DNA and apocarotenoids, as well as their combinations with temozolomide, did not present any significant alterations in the structure of DNA suggesting a possible groove binding interaction. The viscosity analyses verified that ct-DNA interacts with apocarotenoids along with their temozolomide combination through a groove-binding mechanism. This study offers a more comprehensive understanding of the potential mechanism of interaction between ct-DNA and natural compounds with the addition of temozolomide.

Influence of diimine bidentate ligand in the nitrosyl and nitro terpyridine ruthenium complex on the HSA/DNA interaction and antiviral activity

Nitric oxide (NO) acts in different physiological processes, such as blood pressure control, antiparasitic activities, neurotransmission, and antitumor action. Among the exogenous NO donors, ruthenium nitrosyl/nitro complexes are potential candidates for prodrugs, due to their physicochemical properties, such as thermal and physiological pH stability. In this work, we proposed the synthesis and physical characterization of the new nitro terpyridine ruthenium (II) complexes of the type [RuII(L)(NO2)(tpy)]PF6 where tpy = 2,2':6′,2″-terpyridine; L = 3,4-diaminobenzoic acid (bdq) or o-phenylenediamine (bd) and evaluation of influence of diimine bidentate ligand NH.NHq-R (R = H or COOH) in the HSA/DNA interaction as well as antiviral activity. The interactions between HSA and new nitro complexes [RuII(L)(NO2)(tpy)]+ were evaluated. The Ka values for the HSA–[RuII(bdq)(NO2)(tpy)]+ is 10 times bigger than HSA–[RuII(bd)(NO2)(tpy)]+. The sites of interaction between HSA and the complexes via synchronous fluorescence suppression indicate that the [RuII(bdq)(NO2)(tpy)]+ is found close to the Trp-241 residue, while the [RuII(bd)(NO2)(tpy)]+ complex is close to Tyr residues. The interaction with fish sperm fs-DNA using direct spectrophotometric titration (Kb) and ethidium bromide replacement (KSV and Kapp) showed weak interaction in the system fs-DNA-[RuII(bdq)(NO)(tpy)]+. Furthermore, fs-DNA–[RuII(bd)(NO2)(tpy)]+ and fs-DNA–[RuII(bd)(NO)(tpy)]3+ system showed higher intercalation constant. Circular dichroism spectra for fs-DNA–[RuII(bd)(NO2)(tpy)]+ and fs-DNA–[RuII(bd)(NO)(tpy)]3+, suggest semi-intercalative accompanied by major groove binding interaction modes. The [RuII(bd)(NO2)(tpy)]+ and [RuII(bd)(NO)(tpy)]3+ inhibit replication of Zika and Chikungunya viruses based in the nitric oxide release under S-nitrosylation reaction with cysteine viral.

Newly synthesized sulfonamide derivatives explored for DNA binding, enzyme inhibitory, and cytotoxicity activities: a mixed computational and experimental analyses.

The current research work reports the synthesis of three 4-((3-arylthiazolo[3,4-d]isoxazol-5-yl)amino)benzene sulfonamide derivatives with a thaizaole(3,4-d)isoxazole-based fused ring heterocyclic system. The synthesized and characterized derivatives, namely, 4-(3-(2-hydroxy-3-methoxyphenyl)thiazolo[3,4-d]soxazole-5-ylamino)benzenesulfonamide (YM-1), 4-(3-(4-chlorophenyl)isoxazolo[3,4-d]thiazol-5-ylamino)benzenesulfonamide (YM-2), and 4-(3-(3-hydroxyphenyl)isoxazolo[3,4-d]thiazol-5-ylamino)benzenesulfonamide (YM-3) were further explored for their binding interactions with DNA and enzymes (urease and carbonic anhydrase). Cytotoxicity of these derivatives for both healthy (HEK-293) and cancerous (MG-U87) cells was determined by MTT analysis. Both experimental (UV-visible, fluorescence, cyclic voltammetry, and viscometry) and theoretical (molecular docking) profiles suggested that these derivatives are good DNA binders. All the derivatives interacted with DNA via mixed intercalative and groove binding interactions. However, the evaluated DNA binding parameters (K b, ΔG, and n) were comparatively greater for YM-1. Docking data (K b and ΔG) for binding of these derivatives with enzymes also supported that YM-1 was a comparatively better inhibitor for carbonic anhydrase. However, experimentally evaluated IC50 (1.90 ± 0.02 μM) and % inhibition (57.93%) were found to be greater for YM-2 against urease enzyme. All the derivatives show dose-dependent cytotoxicity (70-90%) against MG-U87 cancer cells. Conversely, only one concentration of YM-1 (120 μM) showed less toxicity (50.28% with IC50 of 1.154 ± 0.317 μM) than that of the positive control (52.22%) for healthy cells. Overall findings suggested sulfonamide derivative YM-1 is a better candidate for DNA binding, enzyme inhibition as well as anticancer activity.

Investigation on CT-DNA and Protein Interaction of New Pd(II) Complexes Involving Ceftazidime and 3-Amino-1,2,3-triazole: Synthesis, Characterization, Biological Impact, Anticancer Evaluation, and Molecular Docking Approaches.

Two new palladium (II) complexes, [Pd(CAZ)(OH2 )2 ]2+ (1) and [Pd(3-AT)(OH2 )2 ]2+ (2), (CAZ=ceftazidime, and 3-AT=amitrole) were synthesized and studied for their potential as anticancer drugs with low toxicity and high potency. To fully characterize these complexes, we conducted elemental analysis and FT-IR studies. Furthermore, we irradiated the complexes with Indian 60 Co gamma rays and thoroughly evaluated their antimicrobial properties. Our results demonstrate that the inhibitory activity of complexes was significantly enhanced against (G+) bacteria and fungi. Additionally, we probed the complexes' interaction with CT-DNA and BSA using various techniques, including UV-vis spectroscopy, thermal denaturation, viscometry, gel electrophoresis, and molecular docking studies. Our findings conclusively demonstrate that these complexes possess a strong binding interaction with CT-DNA via minor groove binding and/or electrostatic interactions, as well as excellent binding affinity to BSA. Finally, we conducted a cytotoxicity assay that clearly indicates these complexes hold immense promise as cell growth inhibitors against MCF-7 and HCT-116.

Organotin (2-amino-4-fluorobenzoates): Synthesis, characterization, DFT studies, DNA interaction and cleavage studies

Synthesis of organotin(IV) complexes of 2-amino-4-fluorobenzoic acid (AFA), namely C16H16F2N2O4Sn (1), C22H28F2N2O4Sn (2), C10H14FNO2Sn (3), and C25H20FNO2Sn (4), have been accomplished, and all complexes 1–4 have been characterized using various spectroscopic and analytical techniques, viz. FT–IR and NMR spectroscopy (1H, 13C and 119Sn), ESI–mass spectrometry and elemental analysis. DFT calculations revealed that complexes 1 and 2 exhibited bicapped tetrahedral geometry, while 3 and 4 exhibited distorted tetrahedral environments around tin. Intrinsic binding constants (Kb ≈ 105 M−1) for AFA and complexes 1–4 have been determined by performing UV–vis spectral titration with Calf thymus-DNA (CT-DNA). Further, AFA and complexes 1–4 are luminescent with Kb values of the order of 104 M−1. A significant shift is observed in the circular dichroism (CD) spectra of CT-DNA in the presence of AFA and organotin(IV) complexes 1–4. Based on the UV–vis, fluorescence, and CD studies, it is concluded that AFA and it’s all complexes 1–4 may interact with CT-DNA by minor/major groove binding or electrostatic interaction. Interestingly, triorganotin(IV) complexes 3 and 4 more efficiently cleave the supercoiled form (SC, I) into linear form (L, III) along with the nicked form (NC, II) as compared to complexes 1 and 2, and AFA.

Small Molecule Interactions with Biomacromolecules: DNA Binding Interactions of a Manganese(III) Schiff Base Complex with Potential Anticancer Activities.

A manganese(III) complex, [MnIII(L)(SCN)(enH)](NO3)·H2O (1•H2O) (H2L = 2-((E)-(2-((E)-2-hydroxy-3-methoxybenzylidene-amino)-ethyl-imino)methyl)-6-methoxyphenol), has been synthesized and characterized by single-crystal X-ray diffraction analysis. The interaction of 1•H2O with DNA was studied by monitoring the decrease in absorbance of the complex at λ = 324 nm with the increase in DNA concentration, providing an opportunity to determine the binding constant of the 1•H2O-ct-DNA complex as 5.63 × 103 M-1. Similarly, fluorescence titration was carried out by adding ct-DNA gradually and monitoring the increase in emission intensity at 453 nm on excitation at λex = 324 nm. A linear form of the Benesi-Hildebrand equation yields a binding constant of 4.40 × 103 M-1 at 25 °C, establishing the self-consistency of our results obtained from absorption and fluorescence titrations. The competitive displacement reactions of dyes like ethidium bromide, Hoechst, and DAPI (4',6-diamidine-2'-phenylindole dihydrochloride) from dye-ct-DNA conjugates by 1•H2O were analyzed, and the corresponding KSV values are 1.05 × 104, 1.25 × 104, and 1.35 × 104 M-1 and the Kapp values are 2.16 × 103, 8.34 × 103, and 9.0 × 103 M-1, from which it is difficult to infer the preference of groove binding over intercalation by these DNA trackers. However, the molecular docking experiments and viscosity measurement clearly indicate the preference for minor groove binding over intercalation, involving a change in Gibbs free energy of -8.56 kcal/mol. The 1•H2O complex was then evaluated for its anticancer potential in breast cancer MCF-7 cells, which severely abrogates the growth of the cells in both 2D and 3D mammospheres, indicating its promising application as an anticancer drug through a minor groove binding interaction with ct-DNA.

Novel ternary Pd(II) complexes as potent anticancer drugs for ovarian carcinoma treatment

A novel straightforward method has been introduced to synthesize two new water soluble Pd complexes, [Pd(phd)(AA)]NO3, (phd = 1,10-phenanthroline-5,6-dione; 1, AA = L-isoleucine and 2, AA = L-leucine) using water as a green solvent. Complexes 1 and 2 have been characterized by elemental analysis, FT-IR, 1H NMR spectroscopy and mass spectrometry. A theoretical study of these complexes was conducted using ADME, DFT, and molecular docking. ADME data revealed these complexes as potentially anti-cancer drugs. Fluorescence, UV–Vis, and CD spectroscopy were applied to study the mechanism of DNA interaction. As a result of the fluorescence data, both complexes statically quenched DNA. Based on thermodynamic parameters, Pd(II) complexes and DNA interact via an electrostatic approach and groove binding. CD spectra indicated that both complexes exhibit a slight blue shift with a decrease in intensity across all bands. The experimental data were in agreement with DFT calculations and docking studies. In sum, the mode of binding with DNA intracellular structure is via groove binding and electrostatic interactions. Cytotoxic screening of these compounds carried out against the human ovarian carcinoma cell line A2780SP and cisplatin-resistant variant A2780CP revealed that both complexes showed significantly higher anticancer activity against A2780CP cancer cell line compared to cisplatin. Moreover, all theoretical and experimental data show that complex 2 is more active than complex 1.

Synthesis, DNA-binding, molecular docking, and cytotoxic activity of a new 4-amino-N-(5-selenocyanatothiazol-2-yl) benzenesulfonamide

Triselenium dicyanide (TSD, 2) was combined with 4-amino-N-(thiazol-2-yl) benzenesulfonamide (3) in DMSO to form 4-amino-N-(5-selenocyanatothiazol-2-yl) benzenesulfonamide (4). Acetamide 5 was formed by acetylation of seleno derivative 4 with acetic anhydride. The absorption and fluorescence methods were used to monitor the interaction of compounds 3–5 with the double strain fish sperm deoxyribonucleic acid (dsFS-DNA), revealing a groove binding interaction with a binding constant in the order of 104 M−1. The measured Gibbs free energies, entropies, and enthalpy changes indicated that all interaction processes were spontaneous, with the hydrogen bonding and van der Waals interactions playing important participation for the binding of 3-5 with FS-DNA. Based on the molecular modeling results, the compound binds to the groove of B-DNA with a relative binding energy of -5.06 to -5.94 kcal mol−1. Biological investigations revealed that compound 4 was the most cytotoxic against Panc1 cells with IC50 value of 9.3 µg/mL compared to Doxorubicin (IC50=3.16 µg/mL). It induced apoptosis in Panc1 cells, increasing the death rate by 31.38-fold; it induced total apoptosis by 20.4% (8.2% for early apoptosis, 22.2 % for late apoptosis) compared to 0.65% in the untreated control group. Additionally, compound 4 and 5 exhibited remarkable antioxidant activity with a DPPH inhibition ratio of 71.6 and 56.6% compared to Trolox (96%) at the highest concentration of 100 μM. The findings of this research offer additional useful insights regarding organoselenium compound-DNA interactions as promising cytotoxic agents through apoptosis.

Novel Azapodophyllotoxin Induces DNA Cleavage via Groove Binding: An Advancement in Exploration of Anticancer Activity of a Known Inhibitor of Tubulin Polymerization and Topoisomerase

AbstractThe present study embodies exploration of new potential targets for bioactive azapodophyllotoxins (AZP) that have been mainly considered as inhibitor of tubulin polymerization and topoisomerases. The interaction of a novel AZP, HTDQ, with potential target DNA (calf thymus DNA) has been investigated alongwith its mechanism of action by using combined biophysical spectroscopic techniques and in silico approach. The steady state absorption and fluorescence studies highlights binding interaction of HTDQ with the nucleic acid and the value of Stern Volmer quenching constant (8.07×103 L mol−1) hints towards minor groove binding interaction. The KI quenching studies, helix melting and viscosity measurements further supports our speculation and is substantiated by fluorescence displacement assay using standard minor groove binder, Hoechst 33258. The conformational alterations due to HTDQ‐ctDNA binding is evident from circular dichroism studies and have been further validated from the in silico molecular docking and molecular dynamics simulation studies. Additionally, with a view to get thorough understanding of the mechanism, the DNA cleavage studies have been performed using gel electrophoresis that proved instrumental in determining the ability of HTDQ to damage the structural homogeneity of the nucleic acid.

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.

Exploring heterometallic bridged Pt(II)-Zn(II) complexes as potential antitumor agents

The four novel complexes [{cis-PtCl(NH3)2(μ-4,4′-bipyridyl)ZnCl(terpy)}](ClO4)2 (C1), [{trans-PtCl(NH3)2(μ-4,4′-bipyridyl)ZnCl(terpy)}](ClO4)2 (C2), [{cis-PtCl(NH3)2(μ-pyrazine)ZnCl(terpy)}](ClO4)2 (C3) and [{trans-PtCl(NH3)2(μ-pyrazine)ZnCl(terpy)}](ClO4)2 (C4) (where terpy = 2,2′:6′,2′′-terpyridine) were synthesized and characterized. Acid–base titrations and concentration dependent kinetic measurements for the reactions with biologically relevant ligands such as guanosine-5′-monophosphate (5′-GMP), inosine-5′-monophosphate (5′-IMP) and glutathione (GSH), were studied at pH 7.4 and 37 °C. The binding of the heterometallic bridged cis- or trans-Pt(II)-Zn(II) complexes to calf thymus DNA (CT-DNA) was studied by UV absorption and fluorescence emission spectroscopy and molecular docking. The results indicated that the complexes bind strongly to DNA, through groove binding, hydrogen bonds, and hydrophobic or electrostatic interaction. The possible in vitro DNA protective effect of cis- and trans-Pt-L-Zn complexes has shown that C3 had significant dose-dependent DNA-protective effect and the same ability to inhibit peroxyl as well as hydroxyl radicals. Antiproliferative effect of the complexes, mRNA expression of apoptosis and repair-related genes after treatment in cancer cells indicated that newly synthesized C2 exhibited highly selective cytotoxicity toward colon carcinoma HCT116 cells. Only treatment with trans analog C2 induced effect similar to the typical DNA damaging agent such as cisplatin, characterized by p53 mediated cell response, cell cycle arrest and certain induction of apoptotic related genes. Both cis- and trans-isomers C1 and C2 showed potency to elicit expression of PARP1 mRNA and in vitro DNA binding.

Synthesis, crystallographic, DNA binding, and molecular docking/dynamic studies of a privileged chalcone-sulfonamide hybrid scaffold as a promising anticancer agent

In the present study, a drug-like molecular hybrid structure between chalcone and sulfonamide moieties was synthesized and characterized. The structural peculiarities of the synthesized hybrid were further verified by means of single crystal X-ray crystallography. Furthermore, its biological activity as an anticancer agent was evaluated. The synthesized model of chalcone-sulfonamide hybrid 3 was found to have potent anticancer properties against the studied cancer cell lines. Hence, the in vitro binding interaction of hybrid 3 with Calf thymus DNA (CT-DNA) was studied at a simulated physiological pH to confirm its anticancer activity for the first time. This was investigated by applying different spectroscopic techniques, ionic strength measurements, viscosity measurements, thermodynamics, molecular dynamic simulation and molecular docking studies. The obtained results showed a clear binding interaction between hybrid 3 and CT-DNA with a moderate affinity via a minor groove binding mechanism. The binding constant (Kb ) at 298 K calculated from the Benesi-Hildebrand equation was found to be 3.49 × 104 M−1. The entropy and enthalpy changes (ΔS 0 and ΔH 0) were 204.65 J mol−1 K−1 and 35.08 KJ mol−1, respectively, indicating that hydrophobic interactions constituted the major binding forces. The results obtained from molecular docking and dynamic simulation studies confirmed the minor groove binding interaction and the stability of the formed complex. This study can contribute to further understanding of the molecular mechanism of hybrid 3 as a potential antitumor agent and can also guide future clinical and pharmacological studies for rational drug design with enhanced or more selective activity and greater efficacy. Communicated by Ramaswamy H. Sarma

Synthesis and characterization of the new ligand, 1,2,4-triazino[5,6-b]indol-3-ylimino methyl naphthalene-2-ol and its Ni(II) and Cu(II) complexes: comparative studies of their in vitro DNA and HSA Binding.

A new ligand 1,2,4-triazino[5,6-b]indol-3-ylimino methyl naphthalene-2-ol (HL) was derived from 5H-[1,2,4]triazino[5,6-b]indol-3-amine and 2-hydroxy-1-naphthaldehyde. The metal complexes of the type [Ni(L)(Bipy)]1/2SO4 (1), [Cu(L)(Bipy)(H2O)2]1/2SO4 (2), [Ni(L)(Phen)]1/2SO4 (3) and [Cu(L)(Phen)(H2O)2]1/2SO4 (4) were synthesized. The ligand (HL) and complexes 1-4 were thoroughly characterized by elemental analysis and spectroscopic methods (FT-IR, ToF-MS, 1H NMR, 13C NMR), molar conductance and magnetic moment determination. The Ni(II) complexes 1 and 3 adopt the square planar geometry and Cu(II) complexes 2 and 4 acquire distorted octahedral arrangement. In vitro DNA binding behavior of ligand (HL) and metal complexes 1-4 was explored by fluorescence spectral and ethidium bromide studies. The outcomes reveal that the complexes interact with DNA via non-covalent groove binding and electrostatic interactions. The higher binding constant (K) values of 4.35 × 104 and 9.12 × 104M-1 for complexes 2 and 4 indicate stronger binding ability with DNA. Moreover, in vitro human serum albumin (HSA) binding experiment with HL and complexes 1-4 reveals conformational modulations in the Trp-214 microenvironments in the subdomain IIA pocket.

DNA Optoelectronics: Versatile Systems for On-Demand Functional Electrochemical Applications.

Herein, we propose innovative deoxyribonucleic acid (DNA)-based gels and their applications in diverse optoelectronics. We prepared the optoelectronic DNA-based gels (OpDNA Gel) through molecular complexation, that is, groove binding and ionic interactions of DNA and 1,1'-diheptyl-4,4'-bipyridinium (DHV). This process is feasible even with sequence-nonspecific DNA extracted from nature (e.g., salmon testes), resulting in the expansion of the application scope of DNA-based gels. OpDNA Gel possessed good mechanical characteristics (e.g., high compressibility, thermoplasticity, and outstanding viscoelastic properties) that have not been observed in typical DNA hydrogels. Moreover, the electrochromic (EC) characteristics of DHV were not lost when combined with OpDNA Gel. By taking advantage of the facile moldability, voltage-tunable EC behavior, and biocompatibility/biodegradability of OpDNA Gel, we successfully demonstrated its applicability in a variety of functional electrochemical systems, including on-demand information coding systems, user-customized EC displays, and microorganism monitoring systems. The OpDNA Gel is a promising platform for the application of DNA-based biomaterials in electrochemical optoelectronics.

DNA condensation and formation of ultrathin nanosheets via DNA assisted self-assembly of an amphiphilic fullerene derivative.

DNA nanotechnology propose various assembly strategies to develop novel functional nanostructures utilizing unique interactions of DNA with small molecules, nanoparticles, polymers, and other biomolecules. Although, well defined nanostructures of DNA and amphiphilic small molecules were achieved through hybridization of covalently modified DNA, attaining precise organization of functional moieties through non-covalent interactions remain as a challenging task. Herein, we report mutually assisted assembly of an amphiphilic fullerene derivative and various DNA structures through non-covalent interactions, which leads to initial DNA condensation and subsequent assembly yielding ordered fullerene-DNA nanosheets. The molecular design of the cationic, amphiphilic fullerene derivative (FPy) ensures molecular solubility in the 10% DMSO-PBS buffer system and facile interactions with DNA through groove binding and electrostatic interactions of fullerene moiety and positively charged pyridinium moiety, respectively. The formation of FPy/DNA nanostructures were thoroughly investigated in the presence of λ-DNA, pBR322 plasmid DNA, and single and double stranded 20-mer oligonucleotides using UV-visible spectroscopy, AFM and TEM analysis. λ-DNA and pBR322 plasmid DNA readily condense in presence of FPy leading to micrometer sized few layer nanosheets with significant crystallinity due to ordered arrangement of fullerenes. Similarly, single and double stranded 20-mer oligonucleotides also interact efficiently with FPy and form highly crystalline nanosheets, signifying the role of electrostatic interaction and subsequent charge neutralization in the condensation triggered assembly. However, there is significant differences in the crystallinity and ordered arrangements of fullerenes between these two cases, where longer DNA form condensed structures and less ordered nanosheets while short oligonucleotides lead to more ordered and highly crystalline nanosheets, which could be attributed to the differential DNA condensation. Finally, we have demonstrated the addressability of the assembly using a cyanine modified single strand DNA, which also forms highly crystalline nanosheets and exhibit efficient quenching of the cyanine fluorescence upon self-assembly. These results open up new prospects in the development of functional DNA nanostructures through non-covalent interactions and hence have potential applications in the context of DNA nanotechnology.