Binding Studies Research Articles

Biological and equilibrium studies of Co(II), Cu(II), Zn(II), and Cd(II) complexes of 1‐formyl‐3‐semicarbazide: Docking studies

1‐Formyl‐3‐semicarbazide (FSC, HL) and its metal complexes with Co(II), Cu(II), Zn(II), and Cd(II) ions have been synthesized and characterized by elemental analysis, liquid chromatography‐mass spectrometry (LC–MS), infrared (IR), electronic, nuclear magnetic resonance (NMR) and electron spin resonance (ESR) spectroscopy, thermogravimetric analysis (TGA), magnetic susceptibility, and conductivity measurements. The chelates are non‐electrolytic in nature with distorted octahedral geometry. The kinetic and thermodynamic properties were calculated using the Coats–Redfern relation results in positive enthalpy change values and negative entropy change values. The equilibrium studies of FSC with Co(II), Zn(II), and Cd(II) ion have been carried out by potentiometric pH titrations in 70% v/v DMF‐water medium at 303 K and 0.1 M (KNO3) ionic strength. The study revealed that FSC is monobasic acid with pKa value of 8.84. The stability constants suggested the formation of 1:1 Co(II)‐FSC complex, and Zn(II)‐FSC and Cd(II)‐FSC systems revealed the formation of both 1:1 and 1:2 complexes in the solution. DNA binding studies for the metal chelates have been carried out using electronic absorption spectra, fluorescence emission spectra, and viscosity measurements revealing groove binding for Co(II), and Zn(II) complexes, and intercalation mode of binding for Cu(II)‐FSC complex with CT‐DNA. The Kb values from absorption studies are Co(II)‐FSC = 0.9990 × 102, Cu(II)‐FSC = 2.433 × 104, and Zn(II)‐FSC = 8.277 × 102 M−1, and the KSV values from the competitive fluorescence emission studies are Co(II)‐FSC = 0.19212 and Cu(II)‐FSC = 0.11482 M−1. Molecular docking carried out for both ligand and its Co(II) and Zn(II) complexes also revealed groove mode of binding, and Cu(II) complex showed intercalative mode of binding. The inhibition constants for HL, Co(II), Cu(II), and Zn(II) are 1460, 0.478, 0.122, and 0.194 μM, respectively. The antimicrobial activity has been studied using agar disk diffusion method against Escherichia coli and Bacillus subtilis. FSC has been found to be more active against gram +ve and gram –ve bacteria than its metal chelates.

SEPALLATA-driven MADS transcription factor tetramerization is required for inner whorl floral organ development.

MADS transcription factors are master regulators of plant reproduction and flower development. The SEPALLATA (SEP) subfamily of MADS transcription factors is required for the development of floral organs and plays roles in inflorescence architecture and development of the floral meristem. SEPALLATAs act as organizers of MADS complexes, forming both heterodimers and heterotetramers in vitro. To date, the MADS complexes characterized in angiosperm floral organ development contain at least 1 SEPALLATA protein. Whether DNA binding by SEPALLATA-containing dimeric MADS complexes is sufficient for launching floral organ identity programs, however, is not clear as only defects in floral meristem determinacy were observed in tetramerization-impaired SEPALLATA mutant proteins. Here, we used a combination of genome-wide-binding studies, high-resolution structural studies of the SEP3/AGAMOUS (AG) tetramerization domain, structure-based mutagenesis and complementation experiments in Arabidopsis (Arabidopsis thaliana) sep1 sep2 sep3 and sep1 sep2 sep3 ag-4 plants transformed with versions of SEP3 encoding tetramerization mutants. We demonstrate that while SEP3 heterodimers can bind DNA both in vitro and in vivo and recognize the majority of SEP3 wild-type-binding sites genome-wide, tetramerization is required not only for floral meristem determinacy but also for floral organ identity in the second, third, and fourth whorls.

Fatty acid binding to the human transport proteins FABP3, FABP4, and FABP5 from a Ligand’s perspective

Fatty acid binding proteins (FABPs) are a family of amphiphilic transport proteins with high diversity in terms of their amino acid sequences and binding preferences. Beyond their main biological role as cytosolic fatty acid transporters, many aspects regarding their binding mechanism and functional specializations in human cells remain unclear. In this work, the binding properties and thermodynamics of FABP3, FABP4 and FABP5 were analyzed under various physical conditions. For this purpose, the FABPs were loaded with fatty acids bearing fluorescence or spin probes as model ligands, comparing their binding affinities via microscale thermophoresis (MST) and continuous-wave electron paramagnetic resonance (CW EPR) spectroscopy. The CW EPR spectra of non-covalently bound 5- and 16-DOXYL stearic acid (5/16-DSA) deliver in-depth information about the dynamics and chemical environments of ligands inside the binding pockets of the FABPs. EPR spectral simulations allow the construction of binding curves, revealing two different binding states (‘intermediately’ and ‘strongly’ bound). The proportion of bound 5/16-DSA depends strongly on the FABP concentration and the temperature, but with remarkable differences between the three isoforms. Additionally, the more dynamic state (‘intermediately bound’) seems to dominate at body temperature with thermodynamic preference. The ligand binding studies were supplemented by aggregation studies via dynamic light scattering (DLS) and bioinformatic analyses. Beyond the remarkably fine-tuned binding properties exhibited by each FABP, which were discernible with our EPR-centered approach, the results of this work attest the power of simple spectroscopic experiments to provide new insights into the ligand binding mechanisms of proteins in general on a molecular level.

Experimental biological studies of novel tetradentate hydrazone Cu(II) complexes for potential applications in medicinal chemistry

A series of mononuclear Cu(II) complexes were synthesized using a potential tetradentate hydrazone ligand obtained from the reaction between phenylhydrazine groups and 2,5-thiophenedicarboxaldehyde. The structures of ligands and complexes were elucidated through various spectroscopic techniques, confirming their composition. All complexes were found to adopt four-coordinated geometries, indicating the formation of stable structures. Spectroscopic analysis revealed that the hydrazone ligand coordinated with the Cu(II) metal ions as a dibasic tetradentate ligand by utilizing the phenolic oxygen and azomethine nitrogen atoms. The binding affinity of the complexes with calf thymus DNA (CT-DNA) was investigated using absorption and viscosity measurements, demonstrating their interaction through the intercalation mode. The binding studies showed that the Cu(II) complexes exhibited varying degrees of binding affinity, with Cu(L4) demonstrating the highest affinity, followed by Cu(L1), Cu(L2), and Cu(L3). Moreover, the DNA fragmentation properties of the Cu(II) complexes were evaluated, suggesting their potential utilization in pharmaceutical applications. The obtained results highlight the significance of these novel complexes in the field of medicinal chemistry.

Isoflavones and lysozyme interplay: Molecular insights into binding mechanisms and inhibitory efficacies of isoflavones against protein modification

In this study, we investigated the complexation of bioactive isoflavones, specifically biochanin A (BCA) and genistein (GEN), with hen egg white lysozyme (HEWL) and explored their inhibitory effects on HEWL modification using a combination of multi-spectroscopic and computational methods. The observed binding affinity was of a moderate nature (on the order of 104 M−1), and a static quenching mechanism was identified in the fluorescence quenching process. Notably, the binding constant (Kb) for GEN (4.449 ± 0.262 × 104 M−1) was found to be higher than that for BCA (3.707 ± 0.108 × 104 M−1) towards HEWL. Our spectroscopic measurements, complemented by molecular docking calculations, suggested the involvement of Trp62 in the binding site of the isoflavones within the geometry of HEWL. The micro-environment surrounding the Trp-residues exhibited an increase in hydrophilicity, as indicated by Synchronous fluorescence (SFS) and three-dimensional fluorescence (3D) studies. Interestingly, circular dichroism (CD) studies revealed no marked alteration in the secondary structure of HEWL upon binding with the isoflavones. Furthermore, our investigation into the interaction patterns, employing FTIR and molecular docking studies, revealed a predominance of hydrogen bonding and hydrophobic interactions. Beyond the binding study, the isoflavones demonstrated a promising inhibitory effect on the d-ribose-mediated glycation of HEWL, as well as on HEWL fibrillation, as evidenced by fluorescence emission studies. Our findings not only exhibited an excellent correlation with experimental observations but also provided precise insights into the location and dynamics of isoflavones within the binding site through detailed analyses of molecular docking and molecular dynamics simulation data.

Antibacterial potentials and DNA study of cobalt(II) complexes containing aminophenol Schiff base moiety

The present study was carried out to investigate the effect of substituent groups on the antibacterial activities of 2-aminophenol Schiff bases and their cobalt (II) complexes. Development of new compounds with potential effects against pathogenic organisms has become necessary due to the increase in microbial resistance reported for existing antiseptics and disinfectants. In line with this, new cobalt (II) complexes with Schiff bases derived from 2-aminophenol and p-substituted benzaldehydes were synthesized. The compounds were characterized using elemental analysis, mass spectrometry, atomic absorption spectroscopy, electrospray ionization mass spectrometry, infrared spectroscopy, 1H NMR and electronic absorption spectroscopy. Results indicate that all metal complexes had a 1:2 metal ligand ratio with magnetic moments characteristic of tetrahedral geometry around the metal ion. The Schiff bases and their metal complexes were screened for in-vitro antibacterial activities against 6 human pathogenic bacteria usually found around the hospitals and homes; Escherichia coli (ATCC 8739), Staphylococcus aureus (ATCC 6538), Pseudomonas aeruginosa (ATCC 19582), Bacillus cereus (10702), Enterococcus faecalis (ATCC 29212) and Kribsella pneumonia (ATCC 10031) with ampicillin used as the reference compound. DNA binding study using calf thymus DNA revealed intercalative mode of activity. The result showed that Schiff bases exhibited moderate inhibitory activity against the tested microorganisms while Schiff base metal complexes exhibited higher antibacterial activity when compared to ampicillin. Our results indicate that these complexes can be employed as active ingredients in development of broad-spectrum antibacterial agents.

Association of Metal Cations with the Anti-PF4/Heparin Antibody Response in Heparin-Induced Thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is an antibody-mediated immune response against complexes of heparin and platelet factor 4 (PF4). The electrostatic interaction between heparin and PF4 is critical for the anti-PF4/heparin antibody response seen in HIT. The binding of metal cations to heparin induces conformational changes and charge neutralization of the heparin molecule, and cation-heparin binding can modulate the specificity and affinity for heparin-binding partners. However, the effects of metal cation binding to heparin in the context of anti-PF4/heparin antibody response have not been determined. Here, we utilized inductively coupled plasma mass spectrometry (ICP-MS) to quantify 16 metal cations in patient plasma and tested for correlation with anti-PF4/heparin IgG levels and platelet count after clinical suspicion of HIT in a cohort of heparin-treated patients. The average age of the cohort (n = 32) was 60.53 (SD = 14.31) years old, had a mean anti-PF4/heparin antibody optical density [OD405] of 0.93 (SD = 1.21) units and was primarily female (n = 23). Patients with positive anti-PF4/heparin antibody test results (OD405 ≥ 0.5 units) were younger, had increased weight and BMI, and were more likely to have a positive serotonin release assay (SRA) result compared to antibody negative patients. We observed statistical differences between antibody positive and negative groups for sodium and aluminum and significant correlations of anti-PF4/heparin antibody levels with sodium and silver. While differences in sodium concentrations were associated with antibody positive status and correlated with antibody levels, no replication was performed. Additional studies are warranted to confirm our observed association, including in vitro binding studies and larger observational cohorts.

Studies of Protein Binding to Biomimetic Membranes Using a Group of Uniform Materials Based on Organic Salts Derived From 8-Anilino-1-naphthalenesulfonic Acid.

Tuning the 8-anilino-1-naphthalenesulfonic acid (ANS) structure usually requires harsh conditions and long reaction times, which can result in low yields. Herein, ANS was modified to form an ANS group of uniform materials based on organic salts (GUMBOS), prepared with simple metathesis reactions and distinct cations, namely tetrabutylammonium (N4444), tetrahexylammonium (N6666), and tetrabutylphosphonium (P4444). These ANS-based GUMBOS were investigated as fluorescent probes for membrane binding studies with four proteins having distinct physicochemical properties. Liposomes of 1,2-dimyristoyl-sn-glycero-3-phosphocholine were employed as membrane models as a result of their ability to mimic the structure and chemical composition of cell membranes. Changes in fluorescence intensity were used to monitor protein binding to liposomes, and adsorption data were fitted to a Freundlich-like isotherm. It was determined that [N4444][ANS] and [P4444][ANS] GUMBOS have enhanced optical properties and lipophilicity as compared to parent ANS. As a result, these two GUMBOS were selected for subsequent protein-membrane binding studies. Both [N4444][ANS] and [P4444][ANS] GUMBOS and parent ANS independently reached membrane saturation within the same concentration range. Furthermore, distinct fluorescence responses were observed upon the addition of proteins to each probe, which demonstrates the impact of properties such as lipophilicity on the binding process. The relative maintenance of binding cooperativity and maximum fluorescence intensity suggests that proteins compete with ANS-based probes for the same membrane binding sites. Finally, this GUMBOS-based approach is simple, rapid, and involves relatively small amounts of reagents, making it attractive for high-throughput purposes. These results presented herein can also provide relevant information for designing GUMBOS with ameliorated properties.

Synthesis, Binding and Docking Studies of Indole‐1,3,4‐Thiadiazole Derivatives As Potent Α‐Amylase and Lox Inhibitors

AbstractSeries of indole‐1,3,4‐thiadiazole compounds (IT 1–7) were synthesized and characterized by FT‐IR, 1H NMR, 13C NMR and ESI‐MS spectral data. Further, the compounds (IT 1–7) were screened for antidiabetic, antioxidant and anti‐inflammatory activities. Most of these compounds exhibited moderate to good antidiabetic, antioxidant and anti‐inflammatory activities against α‐amylase enzyme, ABTS and lipoxygenase enzyme, respectively. Among these, IT‐1 displayed the better activity compared to that of standard drugs. The mechanism of binding of IT‐1, IT‐5 and IT‐6 with a transporter protein, human serum albumin was investigated by fluorescence spectroscopic and circular dichroism studies. These compounds quenched the intrinsic fluorescence intensity of HSA and moderate binding was evident from the values of binding constants which are in the order of 105 M−1. The molecular docking studies of the compounds were performed against human pancreatic alpha‐amylase in complex with montbretin A (PDB ID: 4W93). The studied compounds interacted with amino acid residues (ASP197, GLU240 and TYR151) which were similar to that of the reference drug, acarbose. The ADME properties of designed compounds were studied using SwissADME software. All the compounds obeyed Lipinski's rule of five. All the compounds showed low or non‐toxicity towards different toxicity classes as analyzed using ProTox‐II online tool.

Interaction between ammonium based ionic liquids and CRABP I Protein: A microenvironmental spectroscopic analysis

In this article, we have used circular dichroism (CD) and fluorescence to study the physicochemical behaviour of a β-sheet protein, CRABP I, in the presence of ammonium-based ionic liquids (ILs) as a co-solvent. From fluorescence spectroscopy, a rise in intensity was observed in the presence of ionic liquids in the micromolar range, but a reversal in fluorescence intensity at higher concentrations (millimolar range). The microenvironment of aromatic amino acids, tyrosine (Tyr) and tryptophan (Trp), have been compared using synchronous fluorescence data, and the results demonstrate a similar trend in both cases as it has been seen in steady-state spectra. By using CD spectroscopy to examine conformational behaviour, we found that the protein's secondary structure hardly changes at all. Functionality test showed marginal changes in secondary structure of the protein in the presence of ionic liquids. Binding study revealed the contribution of van der waal’s interaction in the case of N2, N4 and N6 and hydrophobic force in the case of N8. The computational study demonstrated that these biophysical behaviours can be accounted for by the hydrophobic interactions between proteins and ionic liquids.

Discovery of Nine Dipeptidyl Peptidase-4 Inhibitors from Coptis chinensis Using Virtual Screening, Bioactivity Evaluation, and Binding Studies.

The objective of this study was to identify multiple alkaloids in Coptis chinensis that demonstrate inhibitory activity against DPP-4 and systematically evaluate their activity and binding characteristics. A combined strategy that included molecular docking, a DPP-4 inhibition assay, surface plasmon resonance (SPR), and a molecular dynamics simulation technique was employed. The results showed that nine alkaloids in Coptis chinensis directly inhibited DPP-4, with IC50 values of 3.44-53.73 μM. SPR-based binding studies revealed that these alkaloids display rapid binding and dissociation characteristics when interacting with DPP-4, with KD values ranging from 8.11 to 29.97 μM. A molecular dynamics analysis revealed that equilibrium was rapidly reached by nine DPP-4-ligand systems with minimal fluctuations, while binding free energy calculations showed that the ∆Gbind values for the nine test compounds ranged from -31.84 to -16.06 kcal/mol. The most important forces for the binding of these alkaloids with DPP-4 are electrostatic interactions and van der Waals forces. Various important amino acid residues, such as Arg125, His126, Phe357, Arg358, and Tyr547, were involved in the inhibition of DPP-4 by the compounds, revealing a mechanistic basis for the further optimization of these alkaloids as DPP-4 inhibitors. This study confirmed nine alkaloids as direct inhibitors of DPP-4 and characterized their binding features, thereby providing a basis for further research and development on novel DPP-4 inhibitors.

Microfibril-associated glycoprotein 4 forms octamers that mediate interactions with elastogenic proteins and cells

Microfibril-associated glycoprotein 4 (MFAP4) is a 36-kDa extracellular matrix glycoprotein with critical roles in organ fibrosis, chronic obstructive pulmonary disease, and cardiovascular disorders, including aortic aneurysms. MFAP4 multimerises and interacts with elastogenic proteins, including fibrillin-1 and tropoelastin, and with cells via integrins. Structural details of MFAP4 and its potential interfaces for these interactions are unknown. Here, we present a cryo-electron microscopy structure of human MFAP4. In the presence of calcium, MFAP4 assembles as an octamer, where two sets of homodimers constitute the top and bottom halves of each octamer. Each homodimer is linked together by an intermolecular disulphide bond. A C34S missense mutation prevents disulphide-bond formation between monomers but does not prevent octamer assembly. The atomic model, built into the 3.55 Å cryo-EM map, suggests that salt-bridge interactions mediate homodimer assembly, while non-polar residues form the interface between octamer halves. In the absence of calcium, an MFAP4 octamer dissociates into two tetramers. Binding studies with fibrillin-1, tropoelastin, LTBP4, and small fibulins show that MFAP4 has multiple surfaces for protein-protein interactions, most of which depend upon MFAP4 octamer assembly. The C34S mutation does not affect these protein interactions or cell interactions. MFAP4 assemblies with fibrillin-1 abrogate MFAP4 interactions with cells.

Binuclear palladacycles with ionisable and non-ionisable tethers as anticancer agents

The search for novel anticancer agents to replace the current platinum-based treatments remains an ongoing process. Palladacycles have shown excellent promise as demonstrated by our previous work which yielded BTC2, a binuclear palladadycle with a non-ionisable polyethylene glycol (PEG) tether. Here, we explore the importance of the PEG-tether length on the anticancer activity of the binuclear palladacycles by comparing three analogous binuclear palladacycles, BTC2, BTC5 and BTC6, in the oestrogen receptor positive MCF7 and triple-negative MDA-MB-231 breast cancer cell lines. In addition, these are compared to another analogue with an ionisable morpholine tether, BTC7. Potent anticancer activity was revealed through cell viability studies (MTT assays) revealed that while BTC6 showed similar potent anticancer activity as BTC2, it was less toxic towards non-cancerous cell lines. Interestingly, BTC7 and BTCF were less potent than the PEGylated palladacycles but showed significantly improved selectivity towards the triple-negative breast cancer cells. Cell death analysis showed that BTC7 and BTCF significantly induced apoptosis in both the cancer cell lines while the PEGylated complexes induced both apoptosis and secondary necrosis. Furthermore, experimental and computational DNA binding studies indicated partial intercalation and groove binding as the modes of action for the PEGylated palladacycles. Similarly, experimental and computational BSA binding studies indicated and specific binding sites in BSA dependent on the nature of the tethers on the complexes.

Organoruthenium metallocycle induced mutation in gld-1 tumor suppression gene in JK1466 strain and appreciable lifespan expansion

Four Ru(II) complexes (A2-A5) were synthesized from the reaction of coumarin Schiff base ligands (7da2-tsc, 7da3-mtsc, 7da4-etsc and 7da5-ptsc) with [RuHCl(CO)(PPh3)3]. The compounds were characterized by FT-IR, UV–Vis, 1H, 13C and 31P NMR, mass spectrometry and crystallographic analysis. Calf Thymus DNA (CT-DNA) binding studies revealed the intercalative mode of binding of the complexes with DNA. The results of Bovine serum albumin (BSA) binding studies established the interaction between BSA followed static quenching mechanism. The cytotoxic effects of the complexes and the ligands were evaluated against breast (MCF-7 and MDA-MB-231) and lung carcinoma cell lines (A549 and NCI-H460) using MTT assay. Complex A4 demonstrated potent cytotoxic effects on both breast and lung cancer cells. Furthermore, morphological observations and FACS analysis showed the decrease in cell density by complex A4 by induced morphological changes and apoptotic body formation and cell death in both breast and lung cancer cells. Moreover, the invertebrate model Caenorhabditis elegans was employed to assess the in vivo anticancer activity of compound A4. The findings indicated that the treatment with A4 reduced tumor development and significantly extended organismal lifespan by 64 % in the tumoral strain JK1466 without adversely affecting essential physiological functions of the worm. Additionally, A4 demonstrated an upregulation of two crucial antioxidant defense genes. Overall, these results suggested that the compound A4 can be a potential candidate with novel chemotherapeutic applications.

Chemoenzymatic Synthesis of Tri-antennary N-Glycans Terminating in Sialyl-Lewisx Reveals the Importance of Glycan Complexity for Influenza A Virus Receptor Binding.

Sialyl-Lewisx (SLex) is involved in immune regulation, human fertilization, cancer, and bacterial and viral diseases. The influence of the complex glycan structures, which can present SLex epitopes, on binding is largely unknown. We report here a chemoenzymatic strategy for the preparation of a panel of twenty-two isomeric asymmetrical tri-antennary N-glycans presenting SLex-Lex epitopes on either the MGAT4 or MGAT5 arm that include putative high-affinity ligands for E-selectin. The N-glycans were prepared starting from a sialoglycopeptide isolated from egg yolk powder and took advantage of inherent substrate preferences of glycosyltransferases and the use of 5'-diphospho-N-trifluoracetylglucosamine (UDP-GlcNHTFA) that can be transferred by branching N-acetylglucosaminyltransferases to give, after base treatment, GlcNH2-containing glycans that temporarily disable an antenna from enzymatic modification. Glycan microarray binding studies showed that E-selectin bound equally well to linear glycans and tri-antennary N-glycans presenting SLex-Lex. On the other hand, it was found that hemagglutinins (HA) of H5 influenza A viruses (IAV) preferentially bound the tri-antennary N-glycans. Furthermore, several H5 HAs preferentially bound to N-glycan presenting SLex on the MGAT4 arm. SLex is displayed in the respiratory tract of several avian species, demonstrating the relevance of investigating the binding of, among others IAVs, to complex N-glycans presenting SLex.

New mono and dinuclear half-sandwiched organoruthenium(II) complexes: Effect of dinuclearity on the biomolecular interaction and cytotoxicity

The present work describes the syntheses and structural characterization of new half sandwiched mono (complex 1) and dinuclear (complex 2) organoruthenium complexes derived from thiosemicarbazone ligand (L1). The molecular structures of compounds were characterized by analytical and multispectroscopic methods which corroborate well with single crystal XRD studies. DFT and TD-DFT studies of compounds revealed that HOMO electron density in L1 is localised on the thiosemicarbazide moiety while the LUMO electron density is evenly distributed over the ligand. However, in complex 1, the HOMO and LUMO is localised on the arene moiety and partially distributed over metal ion while HOMO and LUMO in complex 2 is equally delocalised throughout the complex. The collaborative preliminary DNA binding studies revealed that complexes 1 and 2 exhibited intercalative mode of interaction. The magnitude of DNA binding strength was determined by calculating Kb, K and Ksv values which demonstrated higher DNA binding propensity of complex 2. Furthermore, HSA binding studies of complexes also revealed better binding efficiency of dinuclear complex in contrast to mononuclear complex. The cytotoxic potential of dinuclear complex 2 was examined against triple negative breast cancer cell lines (MDA-MB-468 and MDA-MB-231) via MTT assay.

Fluorescence chemosensor for anion recognition, solvatochromism and protein binding studies based on Schiff- base derivative

A new salicylidene-based chemosensor (E)-N1-(2-hydroxy-3-methoxy-5-nitrobenzylidene)-N2-phenylbenzene-1,2-diamine (MNP) has been developed by condensation of 3-methoxy-5-nitrosalicylaldehyde with N-phenyl-o-phenylenediamine and analysed using FT-IR, 1H-NMR and ESI-MS spectral techniques. The photophysical properties of MNP, including solvatochromism were investigated and the colour changed from bright yellow to red in the presence of water. This MNP specifically detects only Cu2+ with "turn-off" and a colour turned from light yellow to violet in CH3CN/H2O (9/1, v/v) mixture.The optimized geometry of the MNP-Cu complex was analyzed using DFT methods and the results is confirm the formation of the MNP-Cu complex. Besides, the F− and H2PO4−anions are preferentially sensed by the MNP in comparison to other anions, leading a "turn-off" and the colour change from light yellow to dark yellow in the THF medium. From the pH sensor data, the fluorescence intensity increased at pH 4.0 due to protonation of the -OH group. The interaction of the MNP with protein molecules (BSA, HSA) was investigated using absorption and emission spectral methods. The investigation computed values of the binding constant and the Stern-Volmer quenching constant demonstrated that the MNP had a far stronger affinity for BSA than for HSA. The interaction of the MNP with protein molecules was confirmed using docking studies.

Computational design, docking, and molecular dynamics simulation study of RNA helicase inhibitors of dengue virus.

RNA viruses are complex pathogens in terms of their genetic makeup, mutation frequency, and transmission modes. They contain the RNA helicase enzyme, which plays a crucial role in the viral genome replication process. This work aims to develop and screen a potential molecule that could function as a dengue virus (DENV) RNA helicase inhibitor. The present study was performed by taking 26 potential derivatives of gedunin phytochemicals from the PubChem database as ligands. The binding study of the compounds were analyzed by in silico docking method considering DENV RNA helicase enzyme as the receptor. After a thorough analysis of the docking scores, toxicity, and physicochemical properties, compound tetrahydrogedunin was obtained as the best. Based on tetrahydrogedunin molecular structure, 100 drug-like molecules were designed using the Data Warrior tool. After the screening process for drug-likeness and ADMET properties, the derivative number 42 was considered as the promising. Further comparative docking of derivative 42 and a standard inhibitor molecule ST-610 with DENV RNA helicase enzyme showed binding affinity as -10.0 kcal/mol and -9.6 kcal/mol, respectively. The favorable interaction between DENV RNA helicase and derivative 42 was further validated by 50 nanoseconds molecular dynamics simulation and MM-GBSA analysis. Since the antiviral activity of derivative 42 has not been reported till date, the compound was predicted as a novel therapeutic molecule that can act against the dengue virus (DENV) RNA helicase enzyme.

Taking advantage of the interaction between the sulfoxide and heme cofactor to develop indoleamine 2, 3-dioxygenase 1 inhibitors

Taking advantage of key interactions between sulfoxide and heme cofactor, we used the sulfoxide as the anchor functional group to develop two series of indoleamine 2, 3-dioxygenase 1 (IDO1) inhibitors: 2-benzylsulfinylbenzoxazoles (series 1) and 2-phenylsulfinylbenzoxazoles (series 2). In vitro enzymatic screening shows that both series can inhibit the activity of IDO1 in low micromolar (series 1) or nanomolar (series 2) levels. They also show inhibitory selectivity between IDO1 and tryptophan 2, 3-dioxygenase 2. Interestingly, although series 1 is less potent IDO1 inhibitors of these two series, it exhibited stronger inhibitory activity toward kynurenine production in interferon-γ stimulated BxPC-3 cells. Enzyme kinetics and binding studies demonstrated that 2-sulfinylbenzoxazoles are non-competitive inhibitors of tryptophan, and they interact with the ferrous form of heme. These results demonstrated 2-sulfinylbenzoxazoles as type II IDO1 inhibitors. Furthermore, molecular docking studies supports the sulfoxide being of the key functional group that interacts with the heme cofactor. Compound 22 (series 1) can inhibit NO production in a concentration dependent manner in lipopolysaccharides (LPS) stimulated RAW264.7 cells, and can relieve pulmonary edema and lung injury in LPS induced mouse acute lung injury models.

Emphasized DFT, DNA binding, and electrochemical studies of hybrid 1,3,4-thiadiazole-linked chalcone confined via a sulfur bridge

Emphasized DFT, DNA binding, and electrochemical studies of hybrid 1,3,4-thiadiazole-linked chalcone confined via a sulfur bridge