Characterization and Classification In Silico of Peptides with Dual Activity (Antimicrobial and Wound Healing).

The growing challenge of chronic wounds and antibiotic resistance has spotlighted the potential of dual-function peptides (antimicrobial and wound healing) as novel therapeutic strategies. The investigation aimed to characterize and correlate in silico the physicochemical attributes of these peptides with their biological activity. We sourced a dataset of 207 such peptides from various peptide databases, followed by a detailed analysis of their physicochemical properties using bioinformatic tools. Utilizing statistical tools like clustering, correlation, and principal component analysis (PCA), patterns and relationships were discerned among these properties. Furthermore, we analyzed the peptides' functional domains for insights into their potential mechanisms of action. Our findings spotlight peptides in Cluster 2 as efficacious in wound healing, whereas Cluster 1 peptides exhibited pronounced antimicrobial potential. In our study, we identified specific amino acid patterns and peptide families associated with their biological activities, such as the cecropin antimicrobial domain. Additionally, we found the presence of polar amino acids like arginine, cysteine, and lysine, as well as apolar amino acids like glycine, isoleucine, and leucine. These characteristics are crucial for interactions with bacterial membranes and receptors involved in migration, proliferation, angiogenesis, and immunomodulation. While this study provides a groundwork for therapeutic development, translating these findings into practical applications necessitates additional experimental and clinical research.

Characterization of Fe3O4 Nanoparticles for Applications in Catalytic Activity in the Adsorption/Degradation of Methylene Blue and Esterification.

The aim of this study is to evaluate the applicability of the catalytic activity (CA) of the Fe3O4 magnetic system in the adsorption/degradation of methylene blue and esterification. The thermal decomposition method allowed the preparation of Fe3O4 nanoparticles. The crystallites of the Fe3O4 structural phase present an acicular form confirmed by X-ray diffraction. Transmission electron microscopy results identified the acicular shape and agglomeration of the nanoparticles. Mössbauer spectroscopy showed that the spectrum is composed of five components at room temperature, a hyperfine magnetic field distribution (HMFD), two sextets, a doublet, and a singlet. The presence of the HMFD means that a particle size distribution is present. Fluorescence spectroscopy studied the CA of the nanoparticles with methylene blue and found adsorption/degradation properties of the dye. The catalytic activity of the nanoparticles was evaluated in the esterification reaction by comparing the results in the presence and absence of catalyst for the reaction with isobutanol and octanol, where it is observed that the selectivity for the products MIBP and MNOP is favored in the first three hours of reaction.

A Study of the Interaction of a New Benzimidazole Schiff Base with Synthetic and Simulated Membrane Models of Bacterial and Mammalian Membranes.

Biological membranes are complex dynamic systems composed of a great variety of carbohydrates, lipids, and proteins, which together play a pivotal role in the protection of organisms and through which the interchange of different substances is regulated in the cell. Given the complexity of membranes, models mimicking them provide a convenient way to study and better understand their mechanisms of action and their interactions with biologically active compounds. Thus, in the present study, a new Schiff base (Bz-Im) derivative from 2-(m-aminophenyl)benzimidazole and 2,4-dihydroxybenzaldehyde was synthesized and characterized by spectroscopic and spectrometric techniques. Interaction studies of (Bz-Im) with two synthetic membrane models prepared with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and DMPC/1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) 3:1 mixture, imitating eukaryotic and prokaryotic membranes, respectively, were performed by applying differential scanning calorimetry (DSC). Molecular dynamics simulations were also developed to better understand their interactions. In vitro and in silico assays provided approaches to understand the effect of Bz-Im on these lipid systems. The DSC results showed that, at low compound concentrations, the effects were similar in both membrane models. By increasing the concentration of Bz-Im, the DMPC/DMPG membrane exhibited greater fluidity as a result of the interaction with Bz-Im. On the other hand, molecular dynamics studies carried out on the erythrocyte membrane model using the phospholipids POPE (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine), SM (N-(15Z-tetracosenoyl)-sphing-4-enine-1-phosphocholine), and POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) revealed that after 30 ns of interaction, both hydrophobic interactions and hydrogen bonds were responsible for the affinity of Bz-Im for PE and SM. The interactions of the imine with POPG (1-Palmitoyl-2-Oleoyl-sn-Glycero-3-Phosphoglycerol) in the E. coli membrane model were mainly based on hydrophobic interactions.

In Vitro Evaluation of the Potential Pharmacological Activity and Molecular Targets of New Benzimidazole-Based Schiff Base Metal Complexes.

Metal-based drugs, including lanthanide complexes, have been extremely effective in clinical treatments against various diseases and have raised major interest in recent decades. Hence, in this work, a series of lanthanum (III) and cerium (III) complexes, including Schiff base ligands derived from (1H-benzimidazol-2-yl)aniline, salicylaldehyde, and 2,4-dihydroxybenzaldehyde were synthesized and characterized using different spectroscopic methods. Besides their cytotoxic activities, they were examined in human U-937 cells, primate kidney non-cancerous COS-7, and six other, different human tumor cell lines: U251, PC-3, K562, HCT-15, MCF-7, and SK-LU-1. In addition, the synthesized compounds were screened for in vitro antiparasitic activity against Leishmania braziliensis, Plasmodium falciparum, and Trypanosoma cruzi. Additionally, antibacterial activities were examined against two Gram-positive strains (S. aureus ATCC® 25923, L. monocytogenes ATCC® 19115) and two Gram-negative strains (E. coli ATCC® 25922, P. aeruginosa ATCC® 27583) using the microdilution method. The lanthanide complexes generally exhibited increased biological activity compared with the free Schiff base ligands. Interactions between the tested compounds and model membranes were examined using differential scanning calorimetry (DSC), and interactions with calf thymus DNA (CT-DNA) were investigated by ultraviolet (UV) absorption. Molecular docking studies were performed using leishmanin (1LML), cruzain (4PI3), P. falciparum alpha-tubulin (GenBank sequence CAA34101 [453 aa]), and S.aureus penicillin-binding protein 2a (PBP2A; 5M18) as the protein receptors. The results lead to the conclusion that the synthesized compounds exhibited a notable effect on model membranes imitating mammalian and bacterial membranes and rolled along DNA strands through groove interactions. Interactions between the compounds and studied receptors depended primarily on ligand structures in the molecular docking study.

Anticancer activity of pyrimidodiazepines based on 2-chloro-4-anilinoquinazoline: synthesis, DNA binding and molecular docking.

Multidrug resistance to chemotherapy is a critical health problem associated with mutation of the therapeutic target. Therefore, the development of anticancer agents remains a challenge to overcome cancer cell resistance. Herein, a new series of quinazoline-based pyrimidodiazepines 16a-g were synthesized by the cyclocondensation reaction of 2-chloro-4-anilinoquinazoline-chalcones 14a-g with 2,4,5,6-tetraaminopyrimidine. All quinazoline derivatives 14a-g and 16a-g were selected by the U.S. National Cancer Institute (NCI) for testing their anticancer activity against 60 cancer cell lines of different panels of human tumors. Among the tested compounds, quinazoline-chalcone 14g displayed high antiproliferative activity with GI50 values between 0.622-1.81 µM against K-562 (leukemia), RPMI-8226 (leukemia), HCT-116 (colon cancer) LOX IMVI (melanoma), and MCF7 (breast cancer) cancer cell lines. Additionally, the pyrimidodiazepines 16a and 16c exhibited high cytostatic (TGI) and cytotoxic activity (LC50), where 16c showed high cytotoxic activity, which was 10.0-fold higher than the standard anticancer agent adriamycin/doxorubicin against ten cancer cell lines. COMPARE analysis revealed that 16c may possess a mechanism of action through DNA binding that is similar to that of CCNU (lomustine). DNA binding studies indicated that 14g and 16c interact with the calf thymus DNA by intercalation and groove binding, respectively. Compounds 14g, 16c and 16a displayed strong binding affinities to DNA, EGFR and VEGFR-2 receptors. None of the active compounds showed cytotoxicity against human red blood cells.

Antibacterial Activity of a Cationic Antimicrobial Peptide against Multidrug-Resistant Gram-Negative Clinical Isolates and Their Potential Molecular Targets.

Antimicrobial resistance reduces the efficacy of antibiotics. Infections caused by multidrug-resistant (MDR), Gram-negative bacterial strains, such as Klebsiella pneumoniae (MDRKp) and Pseudomonas aeruginosa (MDRPa), are a serious threat to global health. However, cationic antimicrobial peptides (CAMPs) are promising as an alternative therapeutic strategy against MDR strains. In this study, the inhibitory activity of a cationic peptide, derived from cecropin D-like (ΔM2), against MDRKp and MDRPa clinical isolates, and its interaction with membrane models and bacterial genomic DNA were evaluated. In vitro antibacterial activity was determined using the broth microdilution test, whereas interactions with lipids and DNA were studied by differential scanning calorimetry and electronic absorption, respectively. A strong bactericidal effect of ΔM2 against MDR strains, with minimal inhibitory concentration (MIC) and minimal bactericidal concentrations (MBC) between 4 and 16 µg/mL, was observed. The peptide had a pronounced effect on the thermotropic behavior of the 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)/1,2-dimyristoyl-sn-glycero-3-phosphorylglycerol (DMPG) membrane models that mimic bacterial membranes. Finally, the interaction between the peptide and genomic DNA (gDNA) showed a hyperchromic effect, which indicates that ΔM2 can denature bacterial DNA strands via the grooves.

Synthesis, biological evaluation and model membrane studies on metal complexes containing aromatic N,O-chelate ligands.

Novel lanthanide (Ln) compounds [Ln(L)2]Cl.xH2O (Ln = La3+, Ce3+, Sm3+) containing aromatic N,O-chelate ligands [HL1 = 4-amino-2-(1H-benzimidazol-2-yl)phenol; HL2 = 5-amino-2-(1H-benzimidazol-2-yl)phenol] have been synthesized and structurally characterized by elemental analysis, NMR and IR spectroscopy, molar conductance measurements, and mass spectrometry (MS). The spectroscopic data suggested that the benzimidazolyl-phenol ligands act as N,O-chelate ligands through the iminic nitrogen and phenolic oxygen atoms. Elemental analysis indicated that lanthanide compounds were formed in a 1:2 stoichiometry (metal:ligand). In vitro biological evaluation was carried out using these complexes, exhibiting moderate cytotoxicity against six different human tumor cell lines (U251, human glioblastoma; HCT-15, colorectal carcinoma; MCF-7, breast epithelial adenocarcinoma; PC-3, prostate cancer; K562, myelogenous leukemia; SKLU-1, lung carcinoma) and lower toxicity against a non-cancerous cell line (COS-7, primate kidney). In addition, the antibacterial activity of the compounds was assessed against two gram-positive strains (Staphylococcus aureus ATCC 25923, Listeria monocytogenes ATCC 19115) and two gram-negative strains (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27583) using the microdilution method. The results obtained show that the metal complexes exhibit higher biological activity than the free ligands, confirming a synergistic effect. Further benzimidazolyl-phenol derivatives were explored for the detection of bacteria using fluorescence imaging studies. Interestingly, the fluorescent properties of these compounds make them potential candidates to monitor the morphology of bacteria at different compound concentrations. Hence, the interaction of the ligand and complexes with model membranes mimicking those of bacteria was studied by using differential scanning calorimetry (DSC) and molecular dynamics (MD), showing that both compounds decreased the enthalpy of transition in two model membranes as the concentration of the compounds increased. In addition, the main transition temperature was slightly reduced as a result of these interactions.

Síntesis, caracterización y evaluación farmacológica de nuevos complejos metálicos derivados de híbridos heteroaromáticos (benzimidazol/oxadiazol) / Synthesis, characterization and pharmacological evaluation of new metal complexes derived from heteroaromatic hybrids (benzimidazole/oxadiazole)

RESUMEN Este documento reporta la síntesis y caracterización detallada de complejos lantánidos La(III), Ce(III), Nd(III) y Sm(III), con ligandos tridentados derivados de híbridos heteroaromáticos. Los ligandos y sus respectivos complejos metálicos fueron caracterizados mediante diferentes técnicas fisicoquímicas, incluyendo análisis elemental y termogravimétrico; espectroscopias UV-Vis, IR, 1H-NMR y 13C-NMR; mediciones de conductancia molar y espectrometría de masas. Los datos espectrales mostraron que el ligando híbrido se comporta como un ligando tridentado NOO a través de los átomos de nitrógeno y oxígeno de los anillos benzimidazol y oxadiazol, así como del átomo de oxígeno del grupo carbonilo. El análisis elemental y térmico mostró que los complejos metálicos obtenidos tienen una estequiometria 1:2 (metal:ligando). Se evaluó la capacidad antioxidante de los compuestos mediante los ensayos DPPH y medidas electroquímicas (voltametría cíclica y voltametría de onda cuadrada). Los resultados mostraron que los complejos metálicos tienen mayor actividad antioxidante que los ligandos libres. Finalmente, la actividad antibacteriana de los ligandos y sus complejos se determinaron mediante pruebas in vitro contra cepas bacterianas Gram positivas y cepas bacterianas Gram negativas utilizando el método de microdilución en caldo. Los complejos metálicos mostraron mayores actividades antimicrobianas que los ligandos precursores contra algunos de los microorganismos.

SUMMARY This paper reports the synthesis and detailed characterization of lanthanide complexes La(III), Ce(III), Nd(III) y Sm(III) with tridentate ligands derived from heteroaromatic hybrids. The ligands and their metal complexes were characterized by different physicochemical techniques, including elemental and thermogravimetric analysis; UV-Vis, IR, 1H-NMR and 13C-NMR spectroscopy; molar conductance measurements; and mass spectrometry. The spectral data showed that the hybrid ligand behaves as a NOO tridentate ligand through the nitrogen and oxygen atoms of the benzimidazole and oxadiazole rings and the oxygen atom of the carbonyl group. Elemental and thermal analyses indicated that the obtained metal complexes were formed in 1:2 stoichiometry (metal-ligand). The antioxidant capacity of these compounds was evaluated by both DPPH assay and electrochemical measurements (cyclic voltammetry and square wave voltammetry). The results showed that the metal complexes have higher antioxidant activity compare to the free ligands. Finally, the antibacterial activities of the ligands and their complexes were determined by in vitro tests against Gram-positive bacterial strains and Gram-negative bacterial strains using the broth microdilution method. The metal complexes showed greater antimicrobial activities than the precursor ligands against some of the microorganisms.

Studies on the Interaction of Alyteserin 1c Peptide and Its Cationic Analogue with Model Membranes Imitating Mammalian and Bacterial Membranes.

Antimicrobial peptides (AMPs) are effector molecules of the innate immune system and have been isolated from multiple organisms. Their antimicrobial properties are due to the fact that they interact mainly with the anionic membrane of the microorganisms, permeabilizing it and releasing the cytoplasmic content. Alyteserin 1c (+2), an AMP isolated from Alytes obstetricans and its more cationic and hydrophilic analogue (+5) were synthesized using the solid phase method, in order to study the interaction with model membranes by calorimetric and spectroscopic assays. Differential scanning calorimetry (DSC) showed that both peptides had a strong effect when the membrane contained phosphatidylcholine (PC) alone or was mixed with phosphatidylglycerol (PG), increasing membrane fluidization. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) was used to study the secondary structure of the peptide. Peptide +2 exhibited a transition from ß-sheet/turns to ß-sheet/α-helix structures after binding with model membranes, whereas peptide +5 had a transition from aggregation/unordered to ß-sheet/α-helix structures after binding with membrane-contained PC. Interestingly, the latter showed a ß-sheet structure predominantly in the presence of PG lipids. Additionally, molecular dynamics (MD) results showed that the carboxy-terminal of the peptide +5 has the ability to insert into the surface of the PC/PG membranes, resulting in the increase of the membrane fluidity.

Synthesis, antibacterial activity and DNA interactions of lanthanide(IU) complexes of N(4)-substituted thiosemicarbazones / Síntesis, actividad antibacterial e interacciones con DNA de complejos lantánidos (III) de Tiosemicarbazonas N(4)-sustituídas / Síntese, atividade antibacteriana e interações com DNA de complexos lantanídeos (III) de tiosemicarbazonas N(4)-substituídas

Abstract This paper reports the synthesis and detailed characterization of six novel lanthanide complexes of La(III), Eu(III) and Nd(III) with N(4)-substituted thiosemicarbazones derived from the 2-carboxybenzaldehyde. The IR, 1H-NMR and 13C-NMR spectroscopic studies confirmed the coordination of the thiocarbonyl (C=S), azomethine (C=N) and carboxylate (COO-) groups to the metal centers, and the carboxylate was coordinated in a bidentate manner. The elemental and thermal analyses suggest that lanthanide complexes were formed in 1:2 molar ratios (metal:ligand). The molar conductivity values confirmed the non-electrolytic nature of the complexes. The interaction of these complexes with calf thymus DNA (CT-DNA) was investigated by UV absorption and viscosity measurements. It was found that the Eu(HI) and Nd(nI) complexes could roll along the DNA strands through groove interactions. Furthermore, lanthanide complexes could promote the oxidative cleavage of plasmid pBR322 in a high-oxidative stress environment. Finally, the Schiff base ligands (L) and their complexes were evaluated for their antibacterial activities against gram-positive and gram-negative bacteria using a microdilution procedure. The results indicate that the lanthanide complexes exhibit more potent antibacterial activity than the free ligands.

Resumen Este articulo reporta la síntesis y caracterización detallada de seis nuevos complejos lantánidos de La(III), Eu(III) y Nd(III) con tiosemicarbazonas N(4)-sustituidas derivadas del 2-carboxibenzaldehído. Los estudios espectroscópicos de IR, 1H-NMR y 13C-NMR confirmaron la coordinación de los grupos tiocarbonilo (C=S), azometina (C=N) y carboxilato (COO-) a los centros metálicos, y el carboxilato se coordinó de forma bidentada. Los análisis elemental y térmico sugieren que los complejos lantánidos se formaron en proporciones molares 1:2 (metal:ligando). Los valores de conductividad molar confirmaron la naturaleza no eléctrica de los complejos. Por medio de medidas de absorción UV y de viscosidad se investigó la interacción entre estos complejos con DNA de timo de ternera (CT-DNA). Se encontró que los complejos Eu(III) y Nd(III) podrían correr a lo largo de cadenas de DNA a través de interacciones en el surco. Además, los complejos lantánidos podrían promover el clivaje oxidativo del plásmido pBR322 en un ambiente de alto estrés oxidativo. Finalmente, se evaluaron las actividades antibacteriales de las bases de Schiff como ligandos (L) y sus complejos contra bacterias gram-positivas y gram-negativas usando un procedimiento de microdilución. Los resultados indican que los complejos lantánidos exhiben una actividad antibacterial más potente que los ligandos libres.

Resumo Este artigo reporta a síntese e caracterização detalhada de seis novos complexos lantanídeos de La(III), Eu(III) e Nd(III) com tiosemicarbazonas N(4)-substituídas derivadas do 2-carboxibenzaldeído. Os estudos espectroscópicos de IR, 1H-RMN e 13C-RMN confirmaram a coordenação dos grupos tiocarbonilos (C = S), azometina (C=N) e carboxilato (COO-) com os centros metálicos, e o carboxilato se coordenou de forma bidentada. As análises elementares e térmicas sugerem que os complexos lantanídeos se formaram em proporções molares 1:2 (metal:ligante). Os valores de condutividades molar confirmaram a natureza não-elétrica dos complexos. Se avaliou a interação entre estes complexos com DNA de vitela (CT-DNA) por meio de medidas de absorção UV e de viscosidade. Se observou que os complexos Eu(III) e Nd(III) poderiam deslocar-se ao longo da cadeia de DNA através de interações no sulco. Adicionalmente, os complexos lantanídeos poderiam promover a clivagem oxidativa do plasmídeo pBR322 em um ambiente de alto estresse oxidativo. Finalmente, se avaliaram as atividades antibacterianas das bases de Schiff como ligantes (L) e seus complexos contra bactérias gram-positivas e gram- negativas, usando o método de microdiluição. Os resultados indicam que os complexos lantanídeos exibem uma atividade antibacteriana mais potente que os ligantes livres.