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.

The photophysical, photobiological, and DNA/HSA-binding properties of corroles containing carbazole and phenothiazine moieties.

This study characterized four corrole derivatives, namely Cbz-Cor, MetCbz-Cor, PTz-Cor, and PTzEt-Cor, examining their photophysical, electrochemical, photobiological, and biomolecule-binding properties. Experimental photophysical data of absorption and emission elements correlated with a theoretical analysis obtained through time-dependent density functional theory (TD-DFT). As for the photophysical properties, we observed lower fluorescence quantum yields and discernible differences between the excited and ground states, as indicated by Stokes shift values. Natural Transition Orbit (NTO) plots presented high occupied molecular orbital - low unoccupied molecular orbital (HOMO-LUMO) densities around the tetrapyrrolic macrocycle in all examples. Our findings demonstrate that corroles maintain stability in solution and offer photostability (<20 %), predominantly in DMSO(5 %)/Tris-HCl (pH 7.4) buffer solution. Furthermore, the singlet oxygen (1O2) quantum yield and log POW values underscore their potential application in photoinactivation approaches, as these corroles serve as effective ROS generators with more lipophilic features. We also evaluated their biomolecular binding capacity towards salmon sperm DNA and human serum albumin using spectroscopic techniques and molecular docking analysis for sustenance. Concerning biomolecule interaction profiles, the corrole derivatives showed a propensity for interacting in the minor grooves of the double helix DNA due to secondary forces, which were more pronounced in site III of the human serum protein.

Profiling the Interaction between Human Serum Albumin and Clinically Relevant HIV Reverse Transcriptase Inhibitors.

Tenofovir (TFV) is the active form of the prodrugs tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF), both clinically prescribed as HIV reverse transcriptase inhibitors. The biophysical interactions between these compounds and human serum albumin (HSA), the primary carrier of exogenous compounds in the human bloodstream, have not yet been thoroughly characterized. Thus, the present study reports the interaction profile between HSA and TFV, TDF, and TAF via UV-Vis, steady-state, and time-resolved fluorescence techniques combined with isothermal titration calorimetry (ITC) and in silico calculations. A spontaneous interaction in the ground state, which does not perturb the microenvironment close to the Trp-214 residue, is classified as weak. In the case of HSA/TFV and HSA/TDF, the binding is both enthalpically and entropically driven, while for HSA/TAF, the binding is only entropically dominated. The binding constant (Ka) and thermodynamic parameters obtained via ITC assays agree with those obtained using steady-state fluorescence quenching measurements, reinforcing the reliability of the data. The small internal cavity known as site I is probably the main binding pocket for TFV due to the low steric volume of the drug. In contrast, most external sites (II and III) can better accommodate TAF due to the high steric volume of this prodrug. The cross-docking approach corroborated experimental drug-displacement assays, indicating that the binding affinity of TFV and TAF might be impacted by the presence of different compounds bound to albumin. Overall, the weak binding capacity of albumin to TFV, TDF, and TAF is one of the main factors for the low residence time of these antiretrovirals in the human bloodstream; however, positive cooperativity for TAF and TDF was detected in the presence of some drugs, which might improve their residence time (pharmacokinetic profile).

Antiproliferative activity of platinum(II) and copper(II) complexes containing novel biquinoxaline ligands.

Nowadays, cancer represents one of the major causes of death in humans worldwide, which renders the quest for new and improved antineoplastic agents to become an urgent issue in the field of biomedicine and human health. The present research focuses on the synthesis of 2,3,2',3'-tetra(pyridin-2-yl)-6,6'-biquinoxaline) and (2,3,2',3'-tetra(thiophen-2-yl)-6,6'-biquinoxaline) containing copper(II) and platinum(II) compounds as prodrug candidates. The binding interaction of these compounds with calf thymus DNA (CT-DNA) and human serum albumin were assessed with UV titration, thermal decomposition, viscometric, and fluorometric methods. The thermodynamical parameters and the temperature-dependent binding constant (K'b) values point out to spontaneous interactions between the complexes and CT-DNA via the van der Waals interactions and/or hydrogen bonding, except Cu(ttbq)Cl2 for which electrostatic interaction was proposed. The antitumor activity of the complexes against several human glioblastomata, lung, breast, cervix, and prostate cell lines were investigated by examining cell viability, oxidative stress, apoptosis-terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, in vitro migration and invasion, in vitro-comet DNA damage, and plasmid DNA interaction assays. The U87 and HeLa cells were investigated as the cancer cells most sensitive to our complexes. The exerted cytotoxic effect of complexes was attributed to the formation of the reactive oxygen species in vitro. It is clearly demonstrated that Cu(ttbq)Cl2, Pt(ttbq)Cl2, and Pt(tpbq)Cl2 have the highest DNA degradation potential and anticancer effect among the tested complexes by leading apoptosis. The wound healing and invasion analysis results also supported the higher anticancer activity of these two compounds.

Molecular interaction of antiviral drug penciclovir with DNA and HSA insights from experimental and docking studies.

One approach to accelerate the availability of new cancer drugs is to test drugs approved for other conditions as anticancer agents. During recent decades, penciclovir (PNV) has been frequently utilized as a potent antiviral drug, in particular against infections caused by herpes viruses. Many antivirals interact with DNA and change their expression level, so determining the binding mode is of great importance. In our laboratory, we have focused our attention to design improved drugs that target cellular DNA, to understand the mechanism of action at the molecular level, and also to investigate the effect of antiviral drugs as anticancer agents. The results of ct-DNA-PNV interactions at physiological pH using fluorescence spectroscopy, UV-visible absorption spectroscopy, and molecular modeling reveal this drug binds well to ct-DNA through groove binding. The circular dichroism measurements displayed that PNV caused a slight change in the DNA structure which affirmed that the binding of PNV with the DNA occurs through the groove mode. Besides, multi-spectroscopic and molecular docking were used to evaluate how PNV interacts with human serum albumin under physiological conditions. The findings of fluorescence quenching suggested that static quenching was involved in the spontaneous development of HSA-PNV complex through hydrophobic force. The docking simulation results validated the findings of spectroscopic techniques.Communicated by Ramaswamy H. Sarma.

Interaction between a water-soluble anionic porphyrin and human serum albumin unexpectedly stimulates the aggregation of the photosensitizer at the surface of the albumin.

The 5,10,15,20-tetrakis(2,6-difluoro-3-sulfophenyl)porphyrin (TDFPPS4) was reported as a potential photosensitizer for photodynamic therapy. The capacity of the photosensitizers to be carried in the human bloodstream is predominantly determined by its extension of binding, binding location, and binding mechanism to human serum albumin (HSA), influencing its biodistribution and ultimately its photodynamic therapy efficacy in vivo. Thus, the present work reports a biophysical characterization on the interaction between the anionic porphyrin TDFPPS4 and HSA by UV-visible absorption, circular dichroism, steady-state, time-resolved, and synchronous fluorescence techniques under physiological conditions, combined with molecular docking calculations and molecular dynamics simulations. The interaction HSA:TDFPPS4 is spontaneous (ΔG° < 0), strong, and enthalpically driven (ΔH° = -70.1 ± 3.3 kJ mol-1) into subdomain IIA (site I). Curiously, despite the porphyrin binding into an internal pocket, about 50 % of TDFPPS4 structure is still accessible to the solvent, making aggregation in the bloodstream possible. In silico calculations were reinforced by spectroscopic data indicating porphyrin aggregation between bound and unbound porphyrins. This results in an adverse scenario for anionic porphyrins to achieve their therapeutical potential as photosensitizers and control of effective dosages. Finally, a trend of anionic porphyrins to have a combination of quenching mechanisms (static and dynamic) was noticed.

Comparative investigation on interaction between potent antimalarials and human serum albumin using multispectroscopic and computational approaches.

This study performed a comparative investigation to explore the interaction mechanisms between two potential antimalarial compounds, JMI 346 and JMI 105, and human serum albumin (HSA), a vital carrier protein responsible for maintaining important biological functions. Our aim was to assess the pharmacological efficiency of these compounds while comprehensively analyzing their impact on the dynamic behavior and overall stability of the protein. A comprehensive array of multispectroscopic techniques, including UV-Vis. spectroscopy, steady-state fluorescence analysis, synchronous fluorescence spectroscopy, three-dimensional fluorescence and circular dichroism spectroscopy, docking studies, and molecular dynamics simulations, were performed to probe the intricate details of the interaction between the compounds and HSA. Our results revealed that both JMI 346 and JMI 105 exhibited promising pharmacological effectiveness within the context of malaria therapy. However, JMI 346 was found to exhibit a significantly higher affinity and only minor altered impact on HSA, suggesting a more favorable interaction with the protein on the dynamic behavior and overall stability of the protein in comparison to JMI 105. Further studies can build on these results to optimize the drug-protein interaction and enable the development of more potent and targeted antimalarial treatments.

Exploration of Binding Affinities of a 3ß,6ß-Diacetoxy-5α-cholestan-5-ol with Human Serum Albumin: Insights from Synthesis, Characterization, Crystal Structure, Antioxidant and Molecular Docking.

The present study describes the synthesis, characterization, and in vitro molecular interactions of a steroid 3ß,6ß-diacetoxy-5α-cholestan-5-ol. Through conventional and solid-state methods, a cholestane derivative was successfully synthesized, and a variety of analytical techniques were employed to confirm its identity, including high-resolution mass spectrometry (HRMS), Fourier transforms infrared (FT-IR), nuclear magnetic resonance (NMR), elemental analysis, and X-ray single-crystal diffraction. Optimizing the geometry of the steroid was undertaken using density functional theory (DFT), and the results showed great concordance with the data from the experiments. Fluorescence spectral methods and ultraviolet-vis absorption titration were employed to study the in vitro molecular interaction of the steroid regarding human serum albumin (HSA). The Stern-Volmer, modified Stern-Volmer, and thermodynamic parameters' findings showed that steroids had a significant binding affinity to HSA and were further investigated by molecular docking studies to understand the participation of active amino acids in forming non-bonding interactions with steroids. Fluorescence studies have shown that compound 3 interacts with human serum albumin (HSA) through a static quenching mechanism. The binding affinity of compound 3 for HSA was found to be 3.18 × 104 mol-1, and the Gibbs free energy change (ΔG) for the binding reaction was -9.86 kcal mol-1 at 298 K. This indicates that the binding of compound 3 to HSA is thermodynamically favorable. The thermodynamic parameters as well as the binding score obtained from molecular docking at various Sudlow's sites was -8.2, -8.5, and -8.6 kcal/mol for Sites I, II, and III, respectively, supporting the system's spontaneity. Aside from its structural properties, the steroid demonstrated noteworthy antioxidant activity, as evidenced by its IC50 value of 58.5 µM, which is comparable to that of ascorbic acid. The findings presented here contribute to a better understanding of the pharmacodynamics of steroids.

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

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

Synthesis, characterization, HSA binding, molecular docking, cytotoxicity study, and antimicrobial activity of new palladium(II) complexes with propylenediamine derivatives of phenylalanine.

The four new ligands, propylenediamine derivatives of phenylalanine (R2-S,S-pddbaˑ2HCl; L1-L4) and their palladium(II) complexes (C1-C4) were synthesized and characterized by elemental analysis, infrared, 1H and 13C NMR spectroscopy. The interactions of new palladium(II) complexes with human serum albumin (HSA) were studied by fluorescence spectroscopy. All investigated compounds can be transported to target cells by binding to HSA, but complex C4 interacts most strongly. Molecular docking simulations were applied to comprehend the binding of the complex to the molecular target of HSA. Obtained results are in good correlations with experimental data regarding binding affinity by HSA. In vitro cytotoxicity activities were investigated on four tumor cell lines (mouse mammary (4 T1) and colon (CT26), human mammary (MDA-MD-468) and colon (HCT116)) and mouse mesenchymal stem cells as non-tumor control cells. Cytotoxic capacity was determined by MTT test and according to obtained results ligand L4 stands out as the most active and selective compound and as a good candidate for future in vivo testing. Further examination of the ligand L4 and corresponding complex C4 led to the conclusion that both induced cell death mainly by apoptosis. Ligand L4 facilitated cycle arrest in G0/G1 phase and decreased proliferative capacity of tumor cells. In vitro antimicrobial activity for ligands and corresponding Pd(II) complexes was investigated against eleven microorganisms (eight strains of pathogenic bacteria and three yeast species) using microdilution method. The minimum inhibitory concentration and minimum microbicidal concentration were determined.

Characterization of sulfasalazine-bovine serum albumin and human serum albumin interaction by spectroscopic and theoretical approach.

The interaction of sulfasalazine (SZ) with the carrier proteins bovine serum albumin (BSA) and human serum albumin (HSA) was explored by fluorescence, absorption and circular dichroism (CD) spectroscopy along within silicotechniques. The spectral alteration observed in fluorescence, absorption and CD spectra upon the addition of SZ confirmed the complex formation of SZ with BSA and HSA. The inverse temperature dependence behaviour of theKsvvalues as well as the increase in the protein's absorption signals after the addition of SZ indicate that SZ triggered quenching of BSA/HSA fluorescence as the static quenching. The binding affinity (kb) of the order of 106 M-1 was reported towards the BSA-SZ and HSA-SZ association process. Interpretation of thermodynamic data (enthalpy change = -93.85 kJ mol-1and entropy change = -200.81 J mol-1K-1for BSA-SZ system; enthalpy change = -74.12 kJ mol-1and entropy change = -123.90 J mol-1K-1for HSA-SZ system) anticipated that hydrogen bond and van der Waals forces were the main intermolecular forces in the complex stabilization. Inclusion of SZ to BSA/HSA produced microenvironmental perturbations around Tyr and Trp residues. The UV, synchronous and 3D analysis confirmed the structural alteration of proteins after SZ binding, which was supported by CD results. The binding location of SZ in BSA/HSA was detected in Sudlow's site I (subdomain IIA) and the same was revealed by competitive site-marker displacement investigations. Density functional theory study was done to comprehend the feasibility of the analysis and to optimize the structure and energy gap that validated the experimental results. This study is expected to provide deep information about the pharmacology of SZ with its pharmacokinetic properties.

Enantioselective Human Serum Albumin Binding of Apremilast: Liquid Chromatographic, Fluorescence and Molecular Docking Study.

The interaction between human serum albumin (HSA) and apremilast (APR), a novel antipsoriatic drug, was characterized by multimodal analytical techniques including high-performance liquid chromatography (HPLC), fluorescence spectroscopy and molecular docking for the first time. Using an HSA chiral stationary phase, the APR enantiomers were well separated, indicating enantioselective binding between the protein and the analytes. The influence of chromatographic parameters-type and concentration of the organic modifier, buffer type, pH, ionic strength of the mobile phase, flow rate and column temperature-on the chromatographic responses (retention factor and selectivity) was analyzed in detail. The results revealed that the eutomer S-APR bound to the protein to a greater extent than the antipode. The classical van 't Hoff method was applied for thermodynamic analysis, which indicated that the enantioseparation was enthalpy-controlled. The stability constants of the protein-enantiomer complexes, determined by fluorescence spectroscopy, were in accordance with the elution order observed in HPLC (KR-APR-HSA = 6.45 × 103 M-1, KS-APR-HSA = 1.04 × 104 M-1), showing that, indeed, the later-eluting S-APR displayed a stronger binding with HSA. Molecular docking was applied to study and analyze the interactions between HSA and the APR enantiomers at the atomic level. It was revealed that the most favored APR binding occurred at the border between domains I and II of HSA, and secondary interactions were responsible for the different binding strengths of the enantiomers.

Investigation of atropisomeric transformation of a novel PDE4 inhibitor with tetrahydroisoquinoline-based amide group and its primary study of binding to HSA.

In this study a kinetic and thermodynamic atropisomeric transformation due to a hindered rotation around the tetrahydroisoquinoline-based amide group was investigated. Quantum chemistry calculations were applied to investigate the transformation under the gas phase and several solvents with different polarity, and then evaluated by dynamic HPLC determination. It was found that the transformation rate of constants and the half-life time varied under the influence of solvent polarity and temperature and the energies of rotational barrier were determined ranging between 87 and 92 kJ∙mol-1. A primary binding study with HSA confirmed a rapid interconversion under the simulated physiological conditions. It is therefore suggested to take this atropisomeric compound as a racemic mixture for its future drug development.

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 × 104 M-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.

Thermodynamic and structural profiles of multi-target binding of vinblastine in solution.

Structural information about drug-receptor interactions is paramount in drug discovery and subsequent optimization processes. Drugs can bind to multiple potential targets as they contain common chemical entities in their structures. Understanding the details of such interactions offer possibilities for repurposing and developing potent inhibitors of disease pathways. Vinblastine (VLB) is a potent anticancer molecule showing multiple receptor interactions with different affinities and degrees of structural perturbations. We have investigated the multi-target binding profile of VLB with DNA and human serum albumin (HSA) in a dynamic physiological environment using spectroscopic, molecular dynamics simulations, and quantum mechanical calculations to evaluate the structural features, mode, ligand and receptor flexibility, and energetics of complexation. These results confirm that VLB prefers to bind in the major groove of DNA with some inclination toward Thymidine residue and the TR-5 binding site in HSA with its catharanthine half making important contacts with both the receptors. Spectroscopic investigation at multiple temperatures has also proved that VLB binding is entropy driven indicating the major groove and TR-5 binding site of interaction. Finally, the overall binding is facilitated by van der Waals contacts and a few conventional H-bonds. VLB portrays reasonable conformational diversity on binding with multiple receptors.

Bromo-Substituted Diazenyl-pyrazolo[1,5-a]pyrimidin-2-amines: Sonogashira Cross-Coupling Reaction, Photophysical Properties, Bio-interaction and HSA Light-Up Sensor.

A convenient synthesis of a broad series of thirteen examples of alkyne-spacer derivatives 2 from the well-known Sonogashira cross-coupling reaction on diazenyl-pyrazolo[1,5-a]pyrimidin-2-amine compounds 1 is reported. The reactivity of heterocycles 1 due the presence of selected electron-donor (EDG) and electron-withdrawing (EWG) groups attached to different alkynes was evaluated. Also, the reactional versatility due the position variation of the bromo atom at the scaffolds 1 was also investigated. In general, derivatives presented strong absorption bands at the 250-500 nm optical window and UV to cyan emission properties. Also, the redox analysis was recorded by electrochemical cyclic voltammetry technique. For HSA biomacromolecule assays, spectroscopic studies by UV-Vis, steady-state and time-resolved emission fluorescence, and molecular docking calculations evidenced the ability of each compound to establish interactions with human serum albumin (HSA). Finally, the behavior presented for this new class of heterocycles makes them a promising tool as optical sensors for albumins.

Acridine Based N-Acylhydrazone Derivatives as Potential Anticancer Agents: Synthesis, Characterization and ctDNA/HSA Spectroscopic Binding Properties.

A series of novel acridine N-acylhydrazone derivatives have been synthesized as potential topoisomerase I/II inhibitors, and their binding (calf thymus DNA­ctDNA and human serum albumin­HSA) and biological activities as potential anticancer agents on proliferation of A549 and CCD-18Co have been evaluated. The acridine-DNA complex 3b (-F) displayed the highest Kb value (Kb = 3.18 × 103 M−1). The HSA-derivatives interactions were studied by fluorescence quenching spectra. This method was used for the calculation of characteristic binding parameters. In the presence of warfarin, the binding constant values were found to decrease (KSV = 2.26 M−1, Kb = 2.54 M−1), suggesting that derivative 3a could bind to HSA at Sudlow site I. The effect of tested derivatives on metabolic activity of A549 cells evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide or MTT assay decreased as follows 3b(-F) > 3a(-H) > 3c(-Cl) > 3d(-Br). The derivatives 3c and 3d in vitro act as potential dual inhibitors of hTopo I and II with a partial effect on the metabolic activity of cancer cells A594. The acridine-benzohydrazides 3a and 3c reduced the clonogenic ability of A549 cells by 72% or 74%, respectively. The general results of the study suggest that the novel compounds show potential for future development as anticancer agents.

Synthesis and Structure Elucidation of Two Essential Metal Complexes: In-Vitro Studies of Their BSA/HSA-Binding Properties, Docking Simulations, and Anticancer Activities.

Imidazole and tetrazole derivatives are widely used as clinical drugs since they possess a variety of pharmaceutical function. Zinc and iron are essential trace elements of the human body, with less toxicity and good biocompatibility. In this paper, two new essential metal mononuclear complexes [M(H2tmidc)2(H2O)2]·2H2O (M = Zn (1), Fe (2)) were synthesized through the reaction of 2-((1H-tetrazol-1-yl)methylene)-1H-imidazole-4,5-dicarboxylic acid (H3tmidc) and ZnSO4·7H2O or FeSO4·7H2O. The crystal structures were determined by means of the X-ray single crystal diffraction technique. Results from fluorescence investigations show that both complexes could interact with BSA as well as HSA through the static quenching mechanism. van der Waals forces and hydrogen bonds play important roles in the interaction of complexes and BSA/HSA since both ΔH and ΔS values are negative. The results of molecular docking are consistent with those in experimental studies. Furthermore, the anticancer activity of H3tmidc and both complexes against Eca-109 were preliminarily evaluated and the results show that both complexes have better anticancer activity than the corresponding ligand H3tmidc.

Evaluation of Antiproliferative Palladium(II) Complexes of Synthetic Bisdemethoxycurcumin towards In Vitro Cytotoxicity and Molecular Docking on DNA Sequence.

Metallodrugs form a large family of therapeutic agents against cancer, among which is cisplatin, a paradigmatic member. Therapeutic resistance and undesired side effects to Pt(II) related drugs, prompts research on different metal-ligand combinations with potentially enhanced biological activity. We present the synthesis and biological tests of novel palladium(II) complexes containing bisdemethoxycurcumin (BDMC) 1 and 2. Complexes were fully characterized and their structures were determined by X-ray diffraction. Their biological activity was assessed for several selected human tumor cell lines: Jurkat (human leukaemic T-cell lymphoma), HCT-116 (human colorectal carcinoma), HeLa (human cervix epitheloid carcinoma), MCF-7 (human breast adenocarcinoma), MDA-MB-231 (human mammary gland adenocarcinoma), A549 (human alveolar adenocarcinoma), Caco-2 (human colorectal carcinoma), and for non-cancerous 3T3 cells (murine fibroblasts). The cytotoxicity of 1 is comparable to that of cisplatin, and superior to that of 2 in all cell lines. It is a correlation between IC50 values of 1 and 2 in the eight studied cell types, promising a potential use as anti-proliferative drugs. Moreover, for Jurkat cell line, complexes 1 and 2, show an enhanced activity. DFT and docking calculations on the NF-κB protein, Human Serum Albumin (HSA), and DNA were performed for 1 and 2 to correlate with their biological activities.

Alteration of Anticancer and Protein-Binding Properties of Gold(I) Alkynyl by Phenolic Schiff Bases Moieties.

A set of five gold complexes with the general formula Au(PR3)(C≡C-C6H4-4-R') (R = PPh3, R' = -CHO (1), R = PCy3, R' = -CHO (2), R = PPh3, R' = -N=CH-C6H4-2-OH (3), R = PPh3, R' = -N=CH-C6H4-4-OH (4), R = PCy3, R' = -N=CH-C6H4-2-OH (5)) were synthesized and characterized by elemental analysis, 1H-NMR spectroscopy, 31P-NMR spectroscopy, and mass spectrometry. The structures of complexes 2 and 5 were determined by X-ray crystallography. The effects of the structural modifications on the protein binding affinities and anticancer activities of the five gold complexes were assessed. Fluorescence quenching experiments to assess binding to human serum albumin (HSA) revealed that the Schiff base complexes (3, 4, and 5) had binding constants that were superior to their parent aldehyde complexes and highlighted the position of the hydroxy group because complex 4 (4-hydroxy) had a binding constant 6400 times higher than complex 3 (2-hydroxy). The anticancer activities of the complexes against the OVCAR-3 (ovarian carcinoma) and HOP-62 (non-small-cell lung) cancer cell lines showed that the Schiff bases (3-5) were more cytotoxic than the aldehyde-containing complexes (1 and 2). Notably, compound 4 had cytotoxic activity comparable to that of cisplatin against OVCAR-3, demonstrating the significance of the para position for the hydroxy group. Molecular docking studies against the enzyme thioredoxin reductase (TrxR) and human serum albumin were conducted, with docking scores in good agreement with the experimental data. The current study highlights how small structural modifications can alter physiochemical and anticancer properties. Moreover, this simple design strategy using the aldehyde group can generate extensive opportunities to explore new gold(I)-based anticancer drugs via condensation, cyclization, or nucleophilic addition reactions of the aldehyde.