Subdomain IIA Research Articles

Spectroscopic and molecular modeling studies of binding interaction between the new complex of yttrium and 1,10-phenanthroline derivatives with DNA and BSA.

In this study, the 4,9 diazafluoren-9-one ligand and [Y(Daf)2Cl3.OH2] complex were synthesized. The interaction of this complex with DNA and bovine serum albumin (BSA) was investigated by UV-vis and fluorescence spectroscopy. The molecular docking method was used to confirm the experimental results, investigate the type of interaction, and determine the binding site. The binding constant and Stern-Volmer constant were calculated using spectroscopy techniques. The binding constant of the Y-complex with DNA and BSA obtained using the UV-vis technique was 1.61 × 105M-1 and 0.49 × 105M-1, while that obtained using the fluorescence method was 3.39 × 105M-1 and 3.63 × 105M-1, respectively. The results of experimental and theoretical data showed that the interaction between the yttrium complex and DNA and BSA is driven by the hydrogen bond and van der Waals interaction, respectively. The yttrium complex communicates with DNA via the groove interaction. This complex has high binding energy with bovine serum albumin. In addition, the molecular docking results showed that the complex binds to the IIA subdomain of BSA (site I). Finally, anticancer activity of the yttrium complex was studied on MCF-7 and A549 cell lines by using the MTT method. The IC50 values obtained showed that the yttrium complex possesses anticancer activity.

Comprehending the intermolecular interaction of JAK inhibitor fedratinib with bovine serum albumin (BSA)/human alpha-1-acid glycoprotein (HAG): Multispectral methodologies and molecular simulation

The primary coverage of this paper is to investigate the molecular interaction of JAK2 inhibitor, fedratinib (FED) with BSA/HAG proteins through multispectral approaches and molecular docking as well as MD calculation. Arrival at a conclusion, the endogenous fluorescence of BSA/HAG protein was quenched separately in the form of static and mixed quenching. The FED-BSA and FED-HAG complexes with the stoichiometric ratio of 1:1 were formed in the interaction process. And, The Kb values of these complexes were of 104–105 M−1 and 105–106 M−1, respectively, representing that the FED-HAG complex exhibited a comparatively high affinity compared to the FED-BSA complex. It is confimed that FED inserted into the interface area between subdomain IIA and IIB of BSA (marked as site II') and the bucket-shaped hydrophobic cavity of HAG, respectively, resulting in the slight alteration in the secondary structure of BSA/HAG and the micro-environment round Tyr and Trp residues. The expetimental results also confirmed that van der Waals forces (VDW), hydrogen bonds and hydrophobic interaction played a dominant role in the formation of two stable complexes. The above experimental results were supplemented and verified through molecular docking and MD simulation. Meanwhile, the effects of common ions on affinity were explored. This study could shine a light on evaluating the pharmacological properties of the JAK inhibitor FED, understanding the distribution and operation of the drug in the body, and leading to the development of the creation of novel medication devise.

Syntheses, structures, Hirshfeld surface analyses, BSA interactions and molecular docking studies of two leucine Schiff base complexes of oxovanadium(IV)

Two mixed-ligand oxovanadium(IV) complexes with a Schiff base derived from o-vanillin and leucine and 1,10-phenanthroline or 2,2´-bipyridine as a co-ligand, [VO(o-van-Leu)phen] (1) and [VO(o-van-Leu)bipy]·H2O (2), were prepared and structurally characterized by IR spectra, elemental analyses and single-crystal X-ray diffraction. The crystal structures reveal that each oxovanadium(IV) atom in complexes 1 and 2 is surrounded by a N3O3 coordination sphere to form a distorted octahedron with a Schiff base and neutral bidentate ligand phen or bipy. Hirshfeld surface analyses and 2D fingerprint plots indicated that the molecular packings in crystals were dominated by H···H, O···H/H···O, C···H/H···C and π-π interactions. The interactions of both complexes with bovine serum albumin (BSA) were studied by using various spectroscopic and molecular docking methods. BSA binding constants (K), estimated by UV–Vis spectroscopy, were 2.53 × 104M−1 for 1 and 3.18 × 104M−1 for 2, respectively. Together with results of fluorescence and CD spectral studies, it showed that complex 2 has a better affinity for BSA than complex 1. Molecular docking investigation indicated that the two complexes had the similar mode of binding and located within subdomain IIA of BSA. Complex 2 had greater binding activity with the binding free energy (∆Gbinding) of –6.5 kcal/mol than Complex 1 with ∆Gbinding of–5.42 kcal/mol, consisting with the analyses of spectroscopic experimental results.

In silico evaluation of pharmacokinetic parameters, delivery, distribution and anticoagulative effects of new 4,7-dihydroxycoumarin derivative

In this study, pharmacological profiling and investigation of the anticoagulant activity of the newly synthesized coumarin derivative: (E)-3-(1-((4-hydroxy-3-methoxyphenyl)amino)ethylidene)-2,4-dioxochroman-7-yl acetate (L) were performed. The obtained results were compared with the parameters obtained for Warfarin (WF), which is a standard good oral anticoagulant. The estimated high binding affinity of L toward plasma proteins (PPS% value is > 90%) justifies the investigation of binding affinity and comparative analysis of L and WF to Human Serum Albumin (HSA) using the spectrofluorimetric method (296, 303 and 310 K) as well as molecular docking and molecular dynamics simulations. Compound L shows a very good binding affinity especially to the active site of WF (the active site I -subdomain IIA), quenching HSA fluorescence by a static process. Also, the finite element smeared model (Kojic Transport Model, KTM), which includes blood vessels and tissue, was implemented to compute the convective-diffusion transport of L and WF within the liver. Finally, compound L shows a high degree of inhibitory activity toward the VKOR receptor comparable to the inhibitory activity of WF. Stabilization and limited flexibility of amino acid residues in the active site of the VKOR after binding of L and WF indicates a very good inhibitory potential of compound L. The high affinity of the L for the VKOR enzyme (Vitamin K antagonist), as well as the structural similarity to commercial anticoagulants (WF), provide a basis for further studies and potential application in the treatment of venous thrombosis, pulmonary embolism and ischemic heart disease. Communicated by Ramaswamy H. Sarma

Biophysical and docking study on the interaction of anticancer drugs encorafenib and binimetinib with human serum albumin

The utilization of BRAF and MEK inhibitors in combination therapy has demonstrated superior outcomes in the treatment of melanoma as compared to monotherapy. In the present scenario, the combination therapy of Encorafenib (ENC), a BRAF inhibitor, and Binimetinib (BINI), a MEK inhibitor, has been identified as one of the most efficacious treatment modalities for this malignancy. Investigations of protein binding, particularly with human serum albumin (HSA), are essential to understand drug performance and enhance therapeutic outcomes. The investigation of the interplay between small molecule drugs and HSA is of paramount importance, given that such interactions can exert a substantial influence on the pharmacokinetics of these therapeutic agents. The present study aims to bridge these lacunae by implementing a comprehensive approach that integrates fluorescence spectroscopy (FS), isothermal titration calorimetry (ITC), far-ultraviolet circular dichroism (far-UV CD), and molecular simulations. Through analysis of the fluorescence quenching of HSA at three distinct temperatures, it was ascertained that the association constants for the complexes formed between drugs and HSA were of the magnitude of 104 M−1. This suggests that the interactions between the compounds and albumin were moderate and comparable. Simultaneously, the investigation of fluorescence indicated a contrasting binding mechanism for the two inhibitors: ENC predominantly binds to HSA through enthalpic interaction, while BINI/HSA is stabilized by entropic contributions. The data obtained was confirmed through experimental procedures conducted using the ITC method. The results of ligand-competitive displacement experiments indicate that ENC and BINI can bind to HSA within subdomain IIA, specifically Sudlow site I. However, far-UV CD studies show that there are no notable alterations in the structure of HSA upon binding with either of the two inhibitors. Ultimately, the results were supported by computational molecular analysis, which identified the key interactions that contribute to the stabilization of the two ligand/HSA complexes.

Unraveling the Interaction of Synthesized Thienoangelicin Derivative by Fluorescence Studies with Solvents, Bovine Serum Albumin and Metal Ions

AbstractThe growing importance of angelicin derivatives in medicine has prompted us to develop an efficient synthesis strategy for a thienoangelicin derivative, ethyl 8‐methyl‐2‐oxo‐2H‐thieno[2,3‐h]chromene‐3‐carboxylate (MTCE), and investigate its potential applications in spatial probing, therapeutics, and optical sensing. This novel fluorophore, MTCE, exhibits large Stokes shift due to the intramolecular charge separation between the thiophene and coumarin nucleus in the excited state. This indicates its potential for probing spatial polarity. Specific solute‐solvent interactions play a significant role in experimentally calculated excited state dipole moment, including long‐range electrostatic interactions and hydrogen bonding. The multi‐spectroscopic and molecular docking approaches reveal that novel MTCE also interacts in subdomain IIA of BSA by forming ground state complexes following a static quenching mechanism, with the binding constant calculated at ∼104 M−1. The complexation is spontaneous (ΔG ∼−24 kJ mol−1), and enthalpy‐driven (ΔH∼−43 kJ mol−1 and ΔS∼−61 J mol−1), and is primarily mediated by hydrogen bonding and van der Waal forces. Furthermore, the unique fluorescence selectivity of MTCE towards Fe3+ ions under neutral pH conditions, through the formation of a 1 : 1 stoichiometric complex, sets it apart from other common metal ions. Therefore, MTCE holds promising potential for effective utilization in optical sensing applications targeting metal ions.

Imidazole-based optical sensors as a platform for bisulfite sensing and BSA/HSA interaction study. An experimental and theoretical investigation

The fluorescent lapachones were obtained from lapachol, a natural product extracted from the heartwood of Tabebuia sp. (Tecoma). The extracted lapachol was oxidized and cyclized to obtain the compounds β-lapachone and nor-β-lapachone, and treatment with terephthalaldehyde led to the final products with ∼ 60% yield. The photophysical studies showed absorption maxima in the violet region (∼400 nm) and fluorescence emission maxima depending on the solvent, ranging from 430 to 575 nm with a relatively large positive solvatochromism, confirmed by the Lippert-Mataga plot. Theoretical calculations corroborate the experimental observations regarding the ICT mechanism. The imidazoles showed a selective response to bisulfite ion (HSO3−) over other common anions, displaying a large change in both fluorescence and absorption spectra immediately after the addition of bisulfite, proving their potential application in tracing the bisulfite in future biological systems. The binding capacity of the imidazoles with human or bovine serum albumin (HSA and BSA, respectively) is spontaneous, weak (102–103 M−1 range), and subdomains IIA (Site I) and IB (Site III) are the main binding regions for the imidazoles depending on the nature of the metabolite or drug previously complexed with the albumin structure. Overall, both albumins have the same capacity to interact with the imidazoles under study.

Theoretical and experimental investigation of novel quinazoline derivatives: synthesis, photophysical, reactive properties, molecular docking and selective HSA biointeraction

Two new quinazoline derivatives (2a and 2b) were successfully synthesized in this work using the condensation technique in excellent yields. Using spectroscopic techniques and elemental analyses, the compounds were completely characterized. Density functional theory (DFT) computations have been used to examine the title compound’s reactive characteristics. Chemical reactivity was predicted using local reactive descriptors and molecule electrostatic potential. Additionally, Time dependent DFT (TD-DFT) simulations were used to examine the impact of solvents on the photophysical characteristics. The affinity of compounds 2a and 2b for human serum albumin (HSA) was further explored using several electronic spectroscopies. Through static mechanisms, both compounds reduce the intrinsic fluorescence of HSA. It is determined that the HSA-2b complex’s binding constant is significantly greater than the HSA-2a complex. The fluorescence spectrum measurements proved that the HSA underwent structural changes after interaction with these compounds. It was demonstrated by site marker competitive displacement studies that compounds 2a and 2b preferred to bind to site I in HSA subdomain IIA. Additionally, synchronised fluorescence spectra were utilized to analyze how HSA’s conformation changed after interacting with various substances. The molecular docking investigations of these compounds with the three critical HSA binding sites, comprising subdomains IIA, IIIA, and IB, further confirmed the experimental findings. The significant contact between the investigated compounds and HSA was supported by the docking simulations. Communicated by Ramaswamy H. Sarma

Molecular docking of human serum albumin with penicillin G determinants

Background: Human serum albumin (HSA) is the main pharmacokinetic effector of many medications, including penicillin G and its metabolites. An urgent problem of practical medicine is immediate hypersensitivity reactions caused by penicillin toxicity (about 8 % compared to other medications), accompanied by skin pathology, anaphylaxis, and fatality. Objectives: The aim of this study is to describe the structures of penicillin G determinants-HSA complexes and to identify favorable binding sites and the amino acid residues involved in the interaction. Material and Methods: The crystal structure of HSA (ID: 1AO6 from Protein Data Bank) (www.rcsb.org) was chosen as a docking target. Molecular docking methods (AutoDock Tools 1.5.7, AutoDock Vina 1.1.2) were used to gain insight into the interaction of HSA with the major (benzyl penicilloyl G, penicillanic acid) and minor (penicillamine, penicilloic acid, penilloic acid) determinants of penicillin G. Visualization of docking results was implemented in PyMol 2.5. The Protein Plus server (https://proteins.plus) was used to evaluate potential binding pockets. The PLIP tool (https://plip-tool.biotec.tu-dresden.de) was used to identify non-covalent interactions between HSA and its ligands. Results: The molecular docking data indicate that the major determinants of penicillin G are involved in the formation of hydrogen bonds with such HSA residues as Trp214, Arg218, His242, and Asn295; for the minor determinants — Asp108, His146, Tyr148, Ser193, Arg197, Gln204. Both types of determinants are located in the hydrophobic cavity of subdomains IIA and IB. Hydrophobic interactions are present mainly between penicillin G determinants and amino acid residues of subdomain IIIA, such as Ala350, Asp451, Tyr452, and Gln459. Conclusion: The study of penicillin G determinants-HSA complexes is important in the pathogenesis of antibiotic allergy. Identification of specific binding sites can be useful for the development and synthesis of new immunogenic antigens (complexes of major and minor determinants of penicillin G with HSA) that can stimulate the immune system and produce specific antibodies to prevent allergic reactions.

Molecular docking and spectroscopic study of bovine serum albumin interaction with new anticancer Pt complex with isopentyl dithiocarbamate ligand

Although cisplatin is useful in the treatment of cancer, it has a series of side effects that limit its use. Dithiocarbamates reduce the toxicity of platinum due to their structure and the presence of S, and N donating groups. In this article, the interaction of [Pt(bpy)(isopentyl.dtc)]NO3, where bpy is bipyridine and isopentyl.dtc is isopentyl-dithiocarbamate, with BSA, bovine serum albumin has been studied. The molecular binding method, including UV-Vis and fluorescence titration, was carried out in conditions including pH = 7.4 and temperatures of 27 and 37 °C. The negative values of enthalpy (ΔH°b) and entropy (ΔS°b) show that the driving forces of this interaction are hydrogen and van der Waals, and the negative value of the Gibbs free energy, ΔG°b indicates that the interaction proceeds spontaneously. The fluorescence results showed that the quenching mechanism is the static type and the Stern Volmer constant, KSV, was also obtained. The fluorescence titration method data displayed that the quenching mechanism is static. Binding constant (Kb), binding point (n), Hill coefficients, nH, Hill constant, KH, number of binding sites, g, BSA melting temperature, Tm, were also obtained. Finally, the molecular docking method result shows the binding constant, Ki and binding free energy for the platinum complex are −6.53 and 16.39 kcal mol−1, respectively, and also the proper position of binding on BSA can be considered the site I in the subdomain IIA.

Synergistic effect of chlorogenic acid and vitamin D3 (cholecalciferol) on in-vitro glycation may assist in prevention of Polycystic Ovarian Syndrome (PCOS) progression - A biophysical, biochemical and in-silico study

Advanced glycation end products (AGEs) are formed through non-enzymatic glycation, that have been linked to various diseases, including polycystic ovarian syndrome (PCOS) playing a critical role leading to secondary comorbidities such as diabetes-related problems, cardiovascular complications, infertility, etc. As a result, there has been a lot of research into AGE-inhibiting phytochemicals for the remediation and obstruct progression of glycation-related illnesses. The current study is based on in-vitro protein model, in which human serum albumin have been used to investigate the cumulative effect of chlorogenic acid (CGA) and cholecalciferol (vitamin D) on glycation and evaluate their inhibitory impact on AGEs production in the presence of methylglyoxal. Through the application of several biochemical and biophysical techniques, we were able to examine the synergistic impact of both the compounds on albumin structure and its biochemical properties during different stages of glycation. According to Nitro-blue tetrazolium assay results indicate that CGA and vitamin D inhibited fructosamine (early glycation product) production. Moreover, free thiol and lysine residues were significantly increased whereas protein carbonyl levels were significantly decreased. Additive effect of CGA and vitamin D were associated with reduced AGEs fluorescence and increased tryptophan and tyrosine fluorescence. Amadori-albumin after treatment showed some evidence of regaining its alpha-helicity as measured by far-UV CD spectrum. Furthermore, secondary structural alterations were confirmed by Fourier transform infrared spectroscopy (FTIR). ANS (1-anilinonaphthalene-8-sulfonic acid) fluorescence spectra also displayed less revelation of hydrophobic patches. Bilirubin binding capacity was also restored which showed functional recovery of HSA. The electrophoretic mobility was also restored which is portrayed by SDS-PAGE. Additionally, to predict the anti-aggregation potential of CGA and vitamin D, congo red assay and ThT fluorescence was performed which reveal low aggregate formation after treatment. These results corroborated with scanning electron microscopy and confocal microscopy. Docking and simulation results also reveal spontaneous binding of CGA and vitamin D on subdomain IIA of HSA favoring their binding thermodynamically. All the findings suggest that chlorogenic acid and cholecalciferol given in combination might help in prevention of PCOS progression and its related complications.

Characterizing the Interaction of Carmine with Human Serum Albumin Using Biophysical and Molecular Docking Approaches

Carmine (CRM) is regarded as a safe coloring agent derived from the cochineal insect and is used to impart red color in a variety of products ranging from food, beverages, and cosmetics to pharmaceutical drugs. However, various toxicological implications are associated with the use of CRM, viz. anaphylaxis, utricaria, rhinitis, asthma and other cytotoxic and genotoxic ramifications. Therefore, it is imperative to evaluate the toxicity of CRM at the molecular level. A number of biophysical and biochemical methods have been used to examine the impact of CRM on human serum albumin (HSA). The formation of a CRM–HSA complex was revealed by intrinsic fluorescence analysis. The resulting circular dichroism spectra showed that CRM binding reduces the amount of alpha helices present in HSA. The synchronous fluorescence spectroscopy revealed significant microenvironment changes around the tyrosine (Tyr) and tryptophan (Trp) residues in HSA upon CRM binding. The binding of CRM takes place at or close to site I of HSA while also having transient interactions at the subdomain IIA–IIB interfaces determined by the drug displacement and molecular docking studies. Our present research described in the paper, we believe, is significant to understand the CRM-induced toxicity in people.

Probing the interaction of uranyl(VI) complex with bovine serum albumin via in-depth experimental and computational perspectives

Interaction aspects of uranyl(VI) complexes as well as the coordinated ONNO-donor ligand with bovine serum albumin (BSA) were investigated by the fluorescence spectroscopy and computational insights. Under optimal physiological condition, it was observed that there was significant decrease in fluorescence intensity of BSA upon interaction with uranyl(VI) complexes as well as the ligand. The mechanism of interaction between the uranyl(VI) complex and BSA protein was examined by fluorescence measurement. The Stern-Volmer constant, binding affinity, binding constant, standard free energy, and fluorescence lifetime decay profile of BSA in the absence as well as in the presence of uranyl(VI) complex were determined. Furthermore, the conformational binding of uranyl(VI) complexes with BSA protein was explored via molecular docking studies, and confirmed that there is a strong affinity between the Trp-213 residue in the binding pocket of sub-domain IIA and uranyl(VI) complex.

A novel water-soluble Cu(II) gluconate complex inhibits cancer cell growth by triggering apoptosis and ferroptosis related mechanisms

Metal copper complexes have attracted extensive attention as potential alternatives to platinum-based anticancer drugs due to their possible different modes of action. Herein, a new copper(II) gluconate complex, namely [Cu(DPQ)(Gluc)]·2H2O (CuGluc, DPQ = pyrazino[2,3-f][1,10]phenanthroline), with good water-solubility and high anticancer activity was synthesized by using D-gluconic acid (Gluc-2H) as an auxiliary ligand. The complex was well characterized by single-crystal X-ray diffraction analysis, elemental analysis, molar conductivity, and Fourier transform infrared spectroscopy (FTIR). The DNA-binding experiments revealed that CuGluc was bound to DNA by intercalation with end-stacking binding. CuGluc could oxidatively cleave DNA, in which 1O2 and H2O2 were involved. In addition, CuGluc was bound to the IIA subdomain of human serum albumin (HSA) through hydrophobic interaction and hydrogen bonding, showing a good affinity for HSA. The complex showed superior anticancer activity toward several cancer cells than cisplatin in vitro. Further studies indicated that CuGluc caused apoptotic cell death in human liver cancer (HepG2) cells through elevated intracellular reactive oxygen species (ROS) levels, mitochondrial dysfunction, cell cycle arrest, and caspase activation. Interestingly, CuGluc also triggered the ferroptosis mechanism through lipid peroxide accumulation and inhibition of glutathione peroxidase 4 (GPX4) activity. More importantly, CuGluc significantly inhibited tumor growth in vivo, which may benefit from the combined effects of apoptosis and ferroptosis. This work provides a promising strategy to develop highly effective antitumor copper complexes by coordinating with the glucose metabolite D-gluconic acid and exploiting the synergistic effects of apoptosis and ferroptosis mechanisms.

Developing a Multitargeted Anticancer Palladium(II) Agent Based on the His-242 Residue in the IIA Subdomain of Human Serum Albumin.

To obtain next-generation metal drugs that can overcome the deficiencies of platinum (Pt) drugs and treat cancer more effectively, we proposed to develop a multitargeted palladium (Pd) agent to the tumor microenvironment (TME) based on the specific residue(s) of human serum albumin (HSA). To this end, we optimized a series of Pd(II) 2-benzoylpyridine thiosemicarbazone compounds to obtain a Pd agent (5b) with significant cytotoxicity. The HSA-5b complex structure revealed that 5b bound to the hydrophobic cavity in the HSA IIA subdomain and then His-242 replaced a leaving group (Cl) of 5b, coordinating with the Pd center. The in vivo results showed that the 5b/HSA-5b complex had significant capacity of inhibiting tumor growth, and HSA optimized the therapeutic behavior of 5b. In addition, we confirmed that the 5b/HSA-5b complex inhibited tumor growth through multiple actions on different components of TME: killing cancer cells, inhibiting tumor angiogenesis, and activating T cells.

Combined experimental/computational aspects for the molecular interaction of empagliflozin with bovine serum albumin: Quantification and application to human plasma.

Empagliflozin (EMP) is an oral antihyperglycemic agent for type 2 diabetic patients. The molecular binding of EMP to bovine serum albumin (BSA) was elucidated by a combined experimental/computational approach to fulfil the pharmacokinetics and pharmacodynamics gaps of the cited drug for further development. Fluorescence, synchronous, and three-dimensional fluorescence spectroscopy verified that EMP quenched BSA native fluorescence through a dual static/dynamic mechanism that was further supported by Fӧrster resonance energy transfer and ultraviolet absorption spectroscopy. Fourier transform infrared spectroscopy revealed the conformational variations in BSA secondary structure induced by EMP. Thermodynamic properties of the BSA-EMP complex were also investigated, and the hydrophobic interactions' role in the binding process was demonstrated by the computed enthalpy (ΔH =6.558 kJ mol-1 ) and entropy (ΔS = 69.333 J mol-1 K-1 ). Gibbs free energy (ΔG) values were negative at three distinct temperatures, illuminating the spontaneity of this interaction. In addition, molecular docking studies depicted the optimal fitting of EMP to BSA on Site I (sub-domain IIA) through three hydrogen bonds. Additionally, and based on the quenching effect of EMP on BSA fluorescence, this study suggests a simple validated spectrofluorometric method for the quantitation of the studied drug in bulk form and human plasma samples with reasonable recoveries (96.99-103.10%).

Complexities of the Interaction of NiII, PdII and PtII Pyrrole‐Imine Chelates with Human Serum Albumin**

AbstractHuman serum albumin (HSA) efficiently transports drugs in vivo: most are organic. Here, HSA binding affinity and site specificity are shown to depend on the identity of the d8 metal ion in NiII, PdII and PtII chelates of the bis(pyrrole‐imine) ligand H2PrPyrr. Fluorescence quenching data for native and probe‐bound HSA showed sites close to Trp‐214 (subdomain IIA) are targeted. The Stern‐Volmer constants, KSV, ranged from 104 M−1 to 105 M−1 while the affinity constants, Ka, ranged from ∼3.5×103 M−1 to ∼1×106 M−1 at 37 °C, following the order Pd(PrPyrr) > Pt(PrPyrr) > Ni(PrPyrr) > H2PrPyrr. Ligand uptake is enthalpically driven, hinging mainly on London dispersion forces. Induced CD spectra for the protein‐bound ligands could be simulated by hybrid QM:MM TD‐DFT methods, proving that the metal chelates neither decompose nor demetallate after uptake by HSA. Transport and delivery of the metal chelates by HSA in vivo could therefore be feasible.

Histamine derived Schiff bases and corresponding spinaceamines - synthesis, characterization and biological evaluation

The synthesis of eight new histamine-based Schiff bases and cyclic derivatives spinaceamines was accomplished by the reaction of corresponding aldehydes and histamine as amine-counterpart in absolute ethanol. Bearing in mind that the presence of the imino group/or spinaceamine core in the organic molecular scaffold could bring prominent pharmaceutical properties, all synthesised compounds have been screened for their antimicrobial activities against a range of different bacterial and fungal strains and antioxidant activity, as well as for interactions with bovine serum albumin (BSA) and DNA molecules. According to the observed MIC values, the best activity for both, fungal and bacterial species, was displayed by the compound 3c bearing histamine and quinoline moieties in the structure, especially for Staphylococcus aureus. Results obtained in the fluorescence quenching experiments have confirmed ability of tested compounds for DNA and BSA binding, while docking simulations revealed the site I of sub-domain IIA of BSA as a location of binding sites of tested compounds, as well as the minor grove and intercalation interactions with quite similar possibilities to be considered as compounds DNA-binding modes. Further, the molecular docking studies also gave insight into binding modes to the targeted enzymes (CYP51, cytochrome P450 and TyRS) related to the antifungal and antibacterial potential of tested compounds. Two compounds were selected, Schiff base 3c and spinaceamine 4d, to assess the stability of compounds under the physiological conditions (UV-vis spectroscopic study) and in silico ADME properties (SwissADME software), where both compounds have shown the stability after 72 hours in selected medium, and a potential as a drug based on their ADME properties.

In vitro interactions of two pesticides, propazine and quinoxyfen with bovine serum albumin: Spectrofluorometric and molecular docking investigations

Binding mechanisms of two selected pesticides, propazine (PRO) and quinoxyfen (QUI) with bovine serum albumin (BSA) was examined using fluorescence, absorption and molecular docking methods. Intrinsic fluorescence of BSA was quenched in the presence of both PRO and QUI. The quenching was ascertained to be conversely linked to temperature, which suggested the contribution of static quenching process in the PRO–BSA and QUI–BSA complex formations. This results were validated by the enhancement in absorption spectrum of BSA upon binding with PRO and QUI. Binding constant values (Kf = 9.55–0.60 × 10–3 M−1 for PRO–BSA system; Kf = 7.08–5.01 × 102 M−1 for QUI–BSA system) and number of binding site (n) values for the PRO–BSA and QUI–BSA systems at different temperatures affirmed a weak binding strength with a set of equivalent binding sites on BSA. Thermodynamic data obtained for both the PRO–BSA and QUI–BSA interactions predicted that the association process was spontaneous and non-covalent contacts such as hydrophobic interactions, van der Waals forces and hydrogen bonds participated in the binding reactions. This result was further supported by the molecular docking assessments. Three-dimensional spectral results revealed the microenvironmental alterations near tryptophan (Trp) and tyrosine (Tyr) residues in BSA by the addition of PRO and QUI. The docking analysis demonstrated the binding pattern for the PRO–BSA and QUI–BSA systems and disclosed the preferred binding site of both PRO and QUI as site I (subdomain IIA) of BSA.

Interaction of a cobalt(III) complex containing β-amino alcohol with human serum albumin (HSA): Spectroscopic and molecular docking methods

The current work aimed to explore the binding interaction of cobalt(III) complex containing [2-[(E)-({2-[(2-hydroxy ethyl) amino] ethyl} imino) methyl] phenol] ligand with human serum albumin (HSA) in simulative physiological condition (pH 7.4) based on multi-spectroscopic and molecular docking methods. By adding cobalt(III) complex, the HSA absorption was decreased which is a reason for interaction between them. Fluorescence studies and the calculated Ksv and Kq values confirmed that the quenching process is static. Thermodynamic data (ΔH°, and ΔS°) showed that the nature of the interaction forces are hydrophobic and Van der Waals types. A negative sign of Gibbs free energy also indicates the spontaneity of the reaction. The displacement experiments using the site probes warfarin and ibuprofen substantiated that cobalt(III) complex could bind to site I of HSA (subdomain IIA).