Functionalization of ß-cyclodextrin metal-organic frameworks with gelatin and glutamine for drug delivery of curcumin to cancerous cells.

Beta-cyclodextrin Metal-Organic Framework (ß-CD-MOF) is a unique class of porous materials that merges the inherent properties of cyclodextrins with the structural advantages of metal-organic frameworks (MOFs). When combined with the concept of MOFs, which are crystalline structures composed of metal ions or clusters linked by organic ligands, the resulting ß-CD-MOF holds immense potential for various applications, especially in the field of drug delivery. In this study, biocompatible metal-organic frameworks (MOFs) synthesized using ß-Cyclodextrin (ß-CD) and potassium enabled drug delivery of curcumin (CCM) to cancerous cells. Functionalizing ß-CD-MOF with l-glutamine (glutamine-ß-CD-MOF) enhanced cancer cell-specific targeting due to glutamine's essential role in cancer cell proliferation and energy pathways. Amino group functionalization provided further functionalization opportunities. Gelatin coating (gelatin@ß-CD-MOF) facilitated controlled drug release in an acidic medium. High drug loading capacities (52.38-55.63 %) were achieved for ß-CD-MOF@CCM and glutamine-ß-CD-MOF@CCM, leveraging the high porosity and affinity of amine and phenol groups of curcumin. The MTT assay highlighted the specificity and differentiation of glutamine-ß-CD-MOF in targeting cancerous over normal cells. These functionalized ß-CD MOFs efficiently encapsulate curcumin, ensuring controlled drug release and enhanced therapeutic efficacy, particularly in cancer therapy.

Enzyme-responsive mannose-grafted magnetic nanoparticles for breast and liver cancer therapy and tumor-associated macrophage immunomodulation.

BACKGROUND: Chemo-immunotherapy modifies the tumor microenvironment to enhance the immune response and improve chemotherapy. This study introduces a dual-armed chemo-immunotherapy strategy combating breast tumor progression while re-polarizing Tumor-Associated Macrophage (TAM) using prodigiosin-loaded mannan-coated magnetic nanoparticles (PG@M-MNPs). METHODS: The physicochemical properties of one-step synthetized M-MNPs were analyzed, including X-ray diffraction, FTIR, DLS, VSM, TEM, zeta potential analysis, and drug loading content were carried out. Biocompatibility, cancer specificity, cellular uptake, and distribution of PG@M-MNPs were investigated using fluorescence and confocal laser scanning microscopy, and flow cytometry. Furthermore, the expression levels of IL-6 and ARG-1 after treatment with PG and PG@M-MNPs on M1 and M2 macrophage subsets were studied. RESULTS: The M-MNPs were successfully synthesized and characterized, demonstrating a size below 100 nm. The release kinetics of PG from M-MNPs showed sustained and controlled patterns, with enzyme-triggered release. Cytotoxicity assessments revealed an enhanced selectivity of PG@M-MNPs against cancer cells and minimal effects on normal cells. Additionally, immuno-modulatory activity demonstrates the potential of PG@M-MNPs to change the polarization dynamics of macrophages. CONCLUSION: These findings highlight the potential of a targeted approach to breast cancer treatment, offering new avenues for improved therapeutic outcomes and patient survival.

Reconstructing Critical-Sized Mandibular Defects in a Rabbit Model: Enhancing Angiogenesis and Facilitating Bone Regeneration via a Cell-Loaded 3D-Printed Hydrogel-Ceramic Scaffold Application.

In this study, we propose a spatially patterned 3D-printed nanohydroxyapatite (nHA)/beta-tricalcium phosphate (ß-TCP)/collagen composite scaffold incorporating human dental pulp-derived mesenchymal stem cells (hDP-MSCs) for bone regeneration in critical-sized defects. We investigated angiogenesis and osteogenesis in a rabbit critical-sized mandibular defect model treated with this engineered construct. The critical and synergistic role of collagen coating and incorporation of stem cells in the regeneration process was confirmed by including a cell-free uncoated 3D-printed nHA/ß-TCP scaffold, a stem cell-loaded 3D-printed nHA/ß-TCP scaffold, and a cell-free collagen-coated 3D-printed nHA/ß-TCP scaffold in the experimental design, in addition to an empty defect. Posteuthanasia evaluations through X-ray analysis, histological assessments, immunohistochemistry staining, histomorphometry, and reverse transcription-polymerase chain reaction (RT-PCR) suggest the formation of substantial woven and lamellar bone in the cell-loaded collagen-coated 3D-printed nHA/ß-TCP scaffolds. Histomorphometric analysis demonstrated a significant increase in osteoblasts, osteocytes, osteoclasts, bone area, and vascularization compared to that observed in the control group. Conversely, a significant decrease in fibroblasts/fibrocytes and connective tissue was observed in this group compared to that in the control group. RT-PCR indicated a significant upregulation in the expression of osteogenesis-related genes, including BMP2, ALPL, SOX9, Runx2, and SPP1. The findings suggest that the hDP-MSC-loaded 3D-printed nHA/ß-TCP/collagen composite scaffold is promising for bone regeneration in critical-sized defects.

In Vitro Targeted Delivery of Simvastatin and Niacin to Macrophages Using Mannan-Grafted Magnetite Nanoparticles.

Atherosclerosis, a leading cause of mortality worldwide, involves various subsets of macrophages that contribute to its initiation and progression. Current treatment approaches focus on systemic, long-term administration of cholesterol-lowering antioxidants such as statins and certain vitamins, which unfortunately come with prolonged side effects. To overcome these drawbacks, a mannose-containing magnetic nanoparticle (NP) is introduced as a drug delivery system to specifically target macrophages in vitro using simvastatin or niacin and a combinational therapy approach that reduces local inflammation while avoiding unwanted side effects. The synthesized NPs exhibited superparamagnetic behavior, neutrally charged thin coating with a hydrodynamic size of 77.23 ± 13.90 nm, and a metallic core ranging from 15 to 25 nm. Efficient loading of niacin (87.21%) and simvastatin (75.36%) on the NPs was achieved at respective weights of 20.13 and 5.03 (w/w). In the presence of a mannan hydrolyzing enzyme, 79.51% of simvastatin and 67.23% of niacin were released from the NPs within 90 min, with a leakage rate below 19.22%. Additionally, the coated NPs showed no destructive effect on J774A macrophages up to a concentration of 200 µg/mL. Simvastatin-loaded NPs exhibited a minimal increase in IL-6 expression. The low dosage of simvastatin decreased both IL-6 and ARG1 expressions, while niacin and combined simvastatin/niacin increased the level of ARG1 expression significantly. Toxicity evaluations on human umbilical vein endothelial cells and murine liver cells revealed that free simvastatin administration caused significant toxicity, whereas the encapsulated forms of simvastatin, niacin, and a combination of simvastatin/niacin at equivalent concentrations exhibited no significant toxicity. Hence, the controlled release of the encapsulated form of simvastatin and niacin resulted in the effective modulation of macrophage polarization. The delivery system showed suitability for targeting macrophages to atherosclerotic plaque.

Synthesis of Biocompatible Nanoporous ZIF-8-Gum Arabic as a New Carrier for the Targeted Delivery of Curcumin.

The synthesis of biocompatible nanoporous zeolitic imidazolate framework-8 (ZIF-8) was performed in the presence of gum arabic (GA), curcumin (CCM), and folic acid (FA) as a template for the biomineralization process, a natural anticancer component, and a targeting agent, respectively. The synthesis of ZIF-8-GA-CCM-FA was completed in a single step at room temperature in aqueous media with a minimum amount of ethanol at a linker/metal molar ratio of 10. FA was dissolved by the alkaline medium produced by a 2-methyl imidazolium (HmIm) linker without using any toxic organic solvent or additional conjugation agents. The FA-modified carrier can target the folate receptors on Hela cells. To the best of our knowledge, this is the first report about the one-pot encapsulation of CCM and FA in a biocompatible ZIF-8-GA framework in a green solvent. This method enables high CCM loading in the ZIF-8-GA framework structure (ca. 90%) at a short time of 15 min. The effect of CCM concentration was investigated on the size, morphology, and crystallinity of the synthesized structures. The products were characterized with field emission scanning electron microscopy, Brunauer-Emmett-Teller surface area analysis, X-ray diffraction, Fourier transform infrared, and UV-vis spectroscopy techniques. The release rate of CCM from ZIF-8-GA-CCM-FA was studied at different pH values. In vitro drug release of CCM was higher in the acidic medium (pH 5.5, 6.5) compared to physiological pH (7.4). The cytotoxicity of ZIF-8-GA, ZIF-8-GA-CCM, and ZIF-8-GA-CCM-FA structures was evaluated by the standard 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on the three cell lines (fibroblast (normal cell), Hela (FR-positive), and A549 (FR-negative). These results suggested that the ZIF-8-GA-CCM-FA framework can have a promising effect on the targeted treatment of cancer cells.

Water-soluble nickel (II) Schiff base complexes: Synthesis, structural characterization, DNA binding affinity, DNA cleavage, cytotoxicity, and computational studies.

Two water-soluble nickel (II) Schiff base complexes were prepared and their interaction with fish sperm DNA (FS-DNA) was investigated by various methods including UV-vis spectroscopy, fluorescence spectroscopy, cyclic voltammetry, and viscometric measurements. Complex 1: [N,N'-bis{5-[(triphenyl phosphonium chloride)-methyl] salicylidine}-3,4-diaminobenzophenone]nickel(II) perchloride dihydrate: [Ni(5-CH2PPh3-3,4-salophen)] (ClO4)2.2 H2O was synthesized as a new complex and characterized by elemental analysis, IR, 1H NMR, thermal gravimetric analysis (TGA) and UV-vis spectroscopy. Complex 2: sodium [(N,N'-bis(5-sulfosalicyliden)-3, 4-diaminobenzophenone)aqua] nickel(II) hydrate: Na2[Ni (5-SO3-3,4-salbenz)(H2O)]. H2O was already synthesized by our research team, but in this study, its function as a DNA-binding compound was tested, and compared with the results of complex 1-DNA binding. The calculation of different constants using absorption and emission data, all confirmed the stronger binding ability of complex 1 than complex 2 with DNA. Different thermodynamic parameters showed the interactions between DNA and complexes were the type of hydrophobic interaction for complex 1 and electrostatic interaction for complex 2. Also, the negative values of free energy changes proved a spontaneous DNA binding process. Based on cell toxicity assay against two different cell lines including Jurkat and MCF-7, the effect of complex 1 was comparable to cisplatin, and the toxicity mechanism was further justified by bright field microscopy, flow cytometry, and cleavage of DNA in the presence of H2O2. Besides, the docking calculations suggested intercalation after measuring the lowest-energy between the complexes and DNA. For both complexes, all analytical, spectroscopic, and molecular modeling methods supported partial intercalation as the main binding mode between the complexes and DNA.

The effectiveness of antimicrobial photodynamic therapy with prodigiosin against reference strains of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.

Prodigiosin (PG) is a secondary metabolite of bacterial origin that is able to absorb the visible light and plays a role as a photosensitizer in photodynamic therapy (PDT). This in vitro study aimed to investigate the cytotoxicity of PG-mediated PDT against the reference strains of Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and Pseudomonas aeruginosa (P. aeruginosa). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of PG were determined. Each strain was then allocated into four groups as follows: G1: control (no treatment), G2: PG-treated groups that received different PG concentrations (1000-1.95 µM), G3: laser-treated group (wavelength: 520 nm, radiation dose: 187 J/cm2), and G4: PG-mediated PDT groups that were initially treated with different concentrations of PG and were then exposed to laser irradiation in the same way as the previous group. Finally, the number of colony-forming units per milliliter (CFU/mL) was calculated and analyzed using the SPSS software. PG had both bacteriostatic and bactericidal activities on the tested bacteria, with the maximum antibacterial effect being observed against S. aureus. In all bacterial strains, the maximum number of CFUs was observed in the control group followed by the laser-irradiated and PG-treated groups, but the differences were not statistically significant (p > 0.05). However, the utilization of PG-mediated PDT resulted in a significant decrease in the mean number of CFUs in all the tested bacteria (p < 0.0001). PG-mediated PDT had the potential to kill some bacterial strains in the laboratory. Yet, further studies are warranted to confirm its efficacy and safety to be applied in clinical settings.

Immobilization of horseradish peroxidase on lysine-functionalized gum Arabic-coated Fe3O4 nanoparticles for cholesterol determination.

BACKGROUND: Horseradish Peroxidase (HRP) is ranked as one of the most important industrial enzymes that is extensively used in industry. Cholesterol is routinely detected indirectly by cholesterol oxidase in the presence of O2, liberating H2O2 as a by-product. The H2O2 content is determined through the HRP activity in the presence of a redox dye, producing a red colored quinoneimine which can be measured quantitatively. Herein, we have designed a magnetic nanoparticle for reusing and easily separating HRP as the most expensive compartment for the low-cost cholesterol assay. METHODS: The gum Arabic coated magnetic nanoparticles were functionalized with L-lysine linker for maintaining protein flexibility on nanoparticle. Enzyme-loaded nanoparticles were characterized by TEM, FTIR, DLS, VSM and XRD analysis. RESULTS: The immobilization efficiency was ∼65% and the immobilized HRP retained 60% of its activity after 8 times reuse. The optimum pH and thermal stability shifted from 7.0 to 8.0 and 60 to 70 °C after immobilization, respectively. Storage stability of HRP was improved by 10%, at 4 °C for 60 days. Immobilized HRP showed more catalytic activity in presence of Fe2+, Ca2+ and Na+. The designed system has cholesterol detection linearity range from 0.2 to 5.0 mM and detection limit of 0.08 mM and acceptable correlation coefficient of 0.9973 and 0.9982 on sample serum using both chromogens. CONCLUSION: The HRP-loaded magnetic nanoparticles are capable of being used as a cost-effective system for cholesterol determination in laboratory due to its reusability and stability benefits.

Decrease in the inflammatory cytokines of LPS-stimulated PBMCs of patients with atherosclerosis by a TLR-4 antagonist in the co-culture with HUVECs.

Toll-like receptors (TLRs) are among the players of inflammation during atherosclerosis. We assessed the effects of Eritoran, a TLR-4 antagonist, on lipopolysaccharide (LPS)-induced cytokines production by Peripheral Blood Mononuclear Cells (PBMCs) of patients with high-stenosis (HS) (n = 6) and healthy controls (HCs) (n = 6) co-cultured with Human Umbilical Vein Endothelial Cells (HUVECs). LPS stimulation significantly increased the levels of IL-6 (P = 0.007 and P = 0.005), TNF-α (P = 0.006 and P = 0.005), IL-2 (P = 0.007 and P = 0.002), IFN-γ (P = 0.006 and P = 0.003), IL-17A (P = 0.004 and P = 0.003), IL-17F (P = 0.005 and P = 0.003), IL-5 (P = 0.007 and P = 0.005), IL-13 (P = 0.006 and P = 0.005), IL-9 (P = 0.005 and P = 0.005) and IL-21 (P = 0.007 and P = 0.005) in HUVECs co-cultured with HC and HS PBMCs as compared with un-stimulated co-culture condition, respectively. Eritoran treatment (50 µg/mL and 100 µg/mL) significantly reduced the levels of LPS-induced IL-6 (P = 0.007 and P = 0.006; P = 0.007 and P = 0.007), TNF-α (P = 0.005 and P = 0.003; P = 0.007 and P = 0.005), IL-2 (P = 0.007 and P = 0.005; P = 0.005 and P = 0.004), IFN-γ (P = 0.007 and P = 0.005; P = 0.005 and P = 0.004), IL-17A (P = 0.005 and P = 0.002; P = 0.005 and P = 0.002), IL-17F (P = 0.006 and P = 0.006; P = 0.005 and P = 0.005), IL-5 (P = 0.007 and P = 0.006; P = 0.007 and P = 0.007), IL-9 (P = 0.005 and P = 0.005; P = 0.005 and P = 0.005) and IL-21 (P = 0.007 and P = 0.007; P = 0.005 and P = 0.005) in stimulated HUVECs co-cultured with HC and HS PBMCs, compared to un-treated condition, respectively. Our results demonstrate that attenuating effect of Eritoran on the inflammatory responses to LPS is higher in PBMCs of patients with high stenosis, suggesting its potential role in ameliorating inflammatory conditions in atherosclerosis.

CRISPR systems: Novel approaches for detection and combating COVID-19.

Type V and VI CRISPR enzymes are RNA-guided, DNA and RNA-targeting effectors that allow specific gene knockdown. Cas12 and Cas13 are CRISPR proteins that are efficient agents for diagnosis and combating single-stranded RNA (ssRNA) viruses. The programmability of these proteins paves the way for the detection and degradation of RNA viruses by targeting RNAs complementary to its CRISPR RNA (crRNA). Approximately two-thirds of viruses causing diseases contain ssRNA genomes. The Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) has caused the outbreak of the coronavirus disease 2019 (COVID-19), which has infected more than 88 million people worldwide with near 2 million deaths since December 2019. Thus, accurate and rapid diagnostic and therapeutic tools are essential for early detection and treatment of this widespread infectious disease. For us, the CRISPR based platforms seem to be a plausible new approach for an accurate detection and treatment of SARS-CoV-2. In this review, we talk about Cas12 and Cas13 CRISPR systems and their applications in diagnosis and treatment of RNA virus mediated diseases. In continue, the SARS-CoV-2 pathogenicity, and its conventional diagnostics and antivirals will be discussed. Moreover, we highlight novel CRISPR based diagnostic platforms and therapies for COVID-19. We also discuss the challenges of diagnostic CRISPR based platforms as well as clarifying the proposed solution for high efficient selective in vivo delivery of CRISPR components into SARS-CoV-2-infected cells.

Substituted effect on some water-soluble Mn(II) salen complexes: DNA binding, cytotoxicity, molecular docking, DFT studies and theoretical IR & UV studies.

Based on the importance of central metal complexes to interact with DNA, in this research focused on synthesis of some new water soluble Mn(II) complexes 1-4 which modified substituted in ligand at the same position with N, Me, H, and Cl. These complexes were isolated and characterized by elemental analyses, FT-IR, electrospray ionization mass spectrometry (ESI-MS) and UV-vis spectroscopy. DNA binding studies had been studied by using circular dichroism (CD) spectroscopy, UV-vis absorption spectroscopy, cyclic voltammetry (CV), viscosity measurements, emission spectroscopy and gel electrophoresis which proposed the metal buildings go about as effective DNA binders were studied in the presence of Fish-DNA (FS-DNA) which showed the highest binding affinity to DNA with hydrophobic and electron donating substituent. Cell toxicity assays against two human leukemia (Jurkat) and breast cancer (MCF-7) cell lines showed that the complex 3 exhibited a remarkable effects equal to a famous anticancer drug, cisplatin that high cytotoxic activity strongly depend on the hydrophobic substituted ligand. In the theoretical part, density functional theory (DFT) was performed to optimize the geometry of complexes through IR and UV spectra of the complexes that ligand substitution did not affect the geometry and theoretical IR and UV spectra showed good resemblance to the experimental data. The docking studies calculated the lowest-energy between complexes and DNA with the minor grooves mode.

The enzyme-sensitive release of prodigiosin grafted ß-cyclodextrin and chitosan magnetic nanoparticles as an anticancer drug delivery system: Synthesis, characterization and cytotoxicity studies.

In present investigation, two glucose based smart tumor-targeted drug delivery systems coupled with enzyme-sensitive release strategy are introduced. Magnetic nanoparticles (Fe3O4) were grafted with carboxymethyl chitosan (CS) and ß-cyclodextrin (ß-CD) as carriers. Prodigiosin (PG) was used as the model anti-tumor drug, targeting aggressive tumor cells. The morphology, properties and composition and grafting process were characterized by transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FT-IR), vibration sample magnetometer (VSM), X-ray diffraction (XRD) analysis. The results revealed that the core crystal size of the nanoparticles synthesized were 14.2±2.1 and 9.8±1.4nm for ß-CD and CS-MNPs respectively when measured using TEM; while dynamic light scattering (DLS) gave diameters of 121.1 and 38.2nm. The saturation magnetization (Ms) of bare magnetic nanoparticles is 50.10emucm-3, while modification with ß-CD and CS gave values of 37.48 and 65.01emucm-3, respectively. The anticancer compound, prodigiosin (PG) was loaded into the NPs with an encapsulation efficiency of approximately 81% for the ß-CD-MNPs, and 92% for the CS-MNPs. This translates to a drug loading capacity of 56.17 and 59.17mg/100mg MNPs, respectively. Measurement of in vitro release of prodigiosin from the loaded nanocarriers in the presence of the hydrolytic enzymes, alpha-amylase and chitosanase showed that 58.1 and 44.6% of the drug was released after one-hour of incubation. Cytotoxicity studies of PG-loaded nanocarriers on two cancer cell lines, MCF-7 and HepG2, and on a non-cancerous control, NIH/3T3 cells, revealed that the drug loaded nanoparticles had greater efficacy on the cancer cell lines. The selective index (SI) for free PG on MCF-7 and HepG2 cells was 1.54 and 4.42 respectively. This parameter was reduced for PG-loaded ß-CD-MNPs to 1.27 and 1.85, while the SI for CS-MNPs improved considerably to 7.03 on MCF-7 cells. Complementary studies by fluorescence and confocal microscopy and flow cytometry confirm specific targeting of the nanocarriers to the cancer cells. The results suggest that CS-MNPs have higher potency and are better able to target the prodigiosin toxicity effect on cancerous cells than ß-CD-MNPs.

"Click" Chemistry-Tethered Hyaluronic Acid-Based Contact Lens Coatings Improve Lens Wettability and Lower Protein Adsorption.

Improving the wettability of and reducing the protein adsorption to contact lenses may be beneficial for improving wearer comfort. Herein, we describe a simple "click" chemistry approach to surface functionalize poly(2-hydroxyethyl methacrylate) (pHEMA)-based contact lenses with hyaluronic acid (HA), a carbohydrate naturally contributing to the wettability of the native tear film. A two-step preparation technique consisting of laccase/TEMPO-mediated oxidation followed by covalent grafting of hydrazide-functionalized HA via simple immersion resulted in a model lens surface that is significantly more wettable, more water retentive, and less protein binding than unmodified pHEMA while maintaining the favorable transparency, refractive, and mechanical properties of a native lens. The dipping/coating method we developed to covalently tether the HA wetting agent is simple, readily scalable, and a highly efficient route for contact lens modification.

Sulfate as a pivotal factor in regulation of Serratia sp. strain S2B pigment biosynthesis.

In the present work, we investigated the prodiginine family as secondary metabolite members. Bacterial strain S2B, with the ability to produce red pigment, was isolated from the Sarcheshmeh copper mine in Iran. 16S rDNA gene sequencing revealed that the strain was placed in the Serratia genus. Pigment production was optimized using low-cost culture medium and the effects of various physicochemical factors were studied via statistical approaches. Purification of the produced pigment by silica gel column chromatography showed a strong red pigment fraction and a weaker orange band. Mass spectrometry, FT-IR spectroscopy and (1)H NMR analysis revealed that the red pigment was prodigiosin and the orange band was a prodigiosin-like analog, with molecular weights of 323 and 317 Da, respectively. Genotoxicity and cytotoxicity studies confirmed their membership in the prodiginine family. Analysis of the production pattern of the pigments in the presence of different concentrations of ammonium salts revealed the role of sulfate as an important factor in regulation of the pigment biosynthesis pathway. Overall, the data showed that regulation of the pigment biosynthesis pathway in Serratia sp. strain S2B was affected by inorganic micronutrients, particularly the sulfate ions.

Interaction of prodigiosin with HSA and ß-Lg: Spectroscopic and molecular docking studies.

Human serum albumin (HSA) and bovine ß-lactoglobulin (ß-Lg) are both introduced as blood and oral carrier scaffolds with high affinity for a wide range of pharmaceutical compounds. Prodigiosin, a natural three pyrrolic compound produced by Serratia marcescens, exhibits many pharmaceutical properties associated with health benefits. In the present study, the interaction of prodigiosin with HSA and ß-Lg was investigated using fluorescence spectroscopy, circular dichroism (CD) and computational docking. Prodigiosin interacts with the Sudlow's site I of HSA and the calyx of ß-Lg with association constant of 4.41 × 10(4) and 1.99 × 10(4) M(-1) to form 1:1 and 2:3 complexes at 300K, respectively. The results indicated that binding of prodigiosin to HSA and ß-Lg caused strong fluorescence quenching of both proteins through static quenching mechanism. Electrostatic and hydrophobic interactions are the major forces in the stability of PG-HSA complex with enthalpy- and entropy-driving mode, although the formation of prodigiosin-ß-Lg complex is entropy-driven hydrophobic associations. CD spectra showed slight conformational changes in both proteins due to the binding of prodigiosin. Moreover, the ligand displacement assay, pH-dependent interaction and protein-ligand docking study confirmed that the prodigiosin binds to residues located in the subdomain IIA and IIIA of HSA and central calyx of ß-Lg.

Synthesis, characterization, DNA binding, cleavage activity, cytotoxicity and molecular docking of new nano water-soluble [M(5-CH2PPh3-3,4-salpyr)](ClO4)2 (M = Ni, Zn) complexes.

Some new water soluble complexes [N,N'-bis{5-[(triphenyl phosphonium chloride)-methyl]salicylidine}-3,4-diaminopyridine] M(ii), which are formulated as nano-[Zn(5-CH2PPh3-3,4-salpyr)](ClO4)2 (), [Zn(5-CH2PPh3-3,4-salpyr)](ClO4)2 (), nano-[Ni(5-CH2PPh3-3,4-salpyr)](ClO4)2 (), [Ni(5-CH2PPh3-3,4-salpyr)](ClO4)2 (), and [N,N'-bis{5-[(triphenyl phosphonium chloride)-methyl]salicylidine}-2,3-diaminopyridine]Ni(ii) [Ni(5-CH2PPh3-2,3-salpyr)](ClO4)2 () have been isolated and characterized by elemental analysis, FT-IR, (1)H NMR, (13)C NMR, (31)P NMR, and UV-vis spectroscopy. The morphology and size of the nano complexes were determined using FE-SEM and TEM. In vitro DNA binding studies were investigated by UV-vis absorption spectroscopy, viscosity measurements, CD spectroscopy, cyclic voltammetry, emission spectra and gel electrophoresis, which suggest that the metal complexes act as efficient DNA binders. The absorption spectroscopy of the compounds with DNA reveals that the DNA binding affinity (Kb) has this order: > > > > > Ligand. The metal complexes show DNA binding stronger than the ligand, which is expected due to the nature of the metal. The nano complexes display DNA binding stronger than the other complexes which is related to the effect of size on binding affinity and the Ni(ii) complexes reveal DNA binding stronger than the corresponding Zn(ii) analogues, which is expected due to their z* effect and geometry. The prominent double strand DNA cleavage abilities of compound are observed in the absence of H2O2 with efficiencies of more than 50% even at 70 µM complex concentration. Surprisingly, Zn(ii) complexes (compounds & ) exhibit a higher cytotoxicity (IC50: 7.3 & 10.9 µM at 24 h; IC50: 4.6 & 8.7 µM at 48 h) against human hepatoma (HepG2) and HeLa cell lines than the Ni(ii) complexes (compounds , & ) and 5-fluorouracil as control in spite of their inability to cleave DNA. Finally, DNA binding interactions were performed by docking studies. Density functional theory (DFT) studies were performed using the GAUSSIAN 03 program. The DFT method with B3LYP functional, LANL2DZ basis set for metal centers and 6-311g* for other atoms was used. The synthesized compounds and DNA were simulated by molecular docking to explore more details of the ligands conformation and their orientations in the active site of the receptor.