Unveiling the promising anticancer effect of copper-based compounds: a comprehensive review.

Copper is a necessary micronutrient for maintaining the well-being of the human body. The biological activity of organic ligands, especially their anticancer activity, is often enhanced when they coordinate with copper(I) and (II) ions. Copper and its compounds are capable of inducing tumor cell death through various mechanisms of action, including activation of apoptosis signaling pathways by reactive oxygen species (ROS), inhibition of angiogenesis, induction of cuproptosis, and paraptosis. Some of the copper complexes are currently being evaluated in clinical trials for their ability to map tumor hypoxia in various cancers, including locally advanced rectal cancer and bulky tumors. Several studies have shown that copper nanoparticles can be used as effective agents in chemodynamic therapy, phototherapy, hyperthermia, and immunotherapy. Despite the promising anticancer activity of copper-based compounds, their use in clinical trials is subject to certain limitations. Elevated copper concentrations may promote tumor growth, angiogenesis, and metastasis by affecting cellular processes.

Anti-quorum sensing effects of SidA protein on Escherichia coli receptors: in silico analysis.

Quorum sensing enables cell-cell communication in bacteria and regulates biofilm formation. Biofilm production promotes pathogenicity of Escherichia coli and causes infections. However, antibiotic resistance limits conventional treatment efficacy against biofilm infections. Quorum quenching offers an alternative by disrupting quorum sensing signals. Allicin, extracted from garlic, possesses antimicrobial and anti-quorum sensing properties. This study employed molecular docking and dynamics simulations to investigate allicin's interaction with the E. coli quorum sensing system, specifically targeting the cytoplasmic SidA receptor protein. SidA binds to N-acyl-homoserine lactone ligands and regulates quorum sensing in E. coli. The crystal structure of SidA was obtained from the PDB. Molecular docking revealed that allicin competitively binds to the ligand-binding pocket of SidA. Simulations analyzed the effects of allicin binding on SidA stability and affinity for N-acyl-homoserine lactones over 200 ns. Parameters like RMSD, RMSF, and hydrogen bonding indicated SidA was more stable when bound to allicin compared to unbound. Binding free energies suggested allicin reduced SidA's affinity for native ligands. Therefore, allicin binding to SidA alters its conformation and inhibits interaction with N-acyl-homoserine lactones, disrupting quorum sensing signaling and biofilm production in E. coli.Communicated by Ramaswamy H. Sarma.

Synthesis, in silico studies, and in vitro biological evaluation of newly-designed 5-amino-1H-tetrazole-linked 5-fluorouracil analog as a potential antigastric-cancer agent.

5-Fluorouracil (5FU) is a chemotherapy drug used to treat various cancers, such as colorectal, prostate, skin, pancreas, and stomach, as an ointment or solution. However, its consumption has several side effects. Therefore, a new derivative of fluorouracil containing 5-Amino-1H-tetrazole was designed and synthesized through multi-step synthesis to reduce urea excretion and toxicity. The effectiveness of the synthesized drug on the Adenocarcinoma gastric cell line (AGS) gastric cancer cell line was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test, which showed that the new 5-fluorouracil (5FU) analog, with an IC50 of 15.67 µg/mL, is more effective in inhibiting the proliferation of AGS cells after 24 h compared to both synthesized and reported 5FU. In addition, In-silico studies showed that the new 5FU derivative based on amino tetrazole, with a binding energy of -7.2 kcal/mol, exhibits greater anti-cancer activity against the BCL2 enzyme than 5FU, with a binding energy of - 4.8 kcal/mol. It is predicted that the new 5FU derivative will be effective in treating gastric and colorectal cancers. The new derivative of the 5-fluorouracil drug was characterized and identified using FTIR and NMR spectroscopy.Communicated by Ramaswamy H. Sarma.

Effect of the extra-nuclear cation on the cytotoxicity and mechanism of action of pyridine-2,6-dicarboxylate Ga(III) complexes.

Two Ga(III) complexes (C1) and (C2) were prepared by the one-pot reaction of pyridine-2,6-dicarboxylic acid and aminopyridine derivatives with gallium(III) nitrate octahydrate. The compounds were characterized by single-crystal X-ray diffraction. The distorted octahedral geometry was confirmed by crystallographic data for both complexes. The study of the in vitro cytotoxicity of the compounds showed that the presence of different extra-nuclear cations can affect the cytotoxicity of the same anionic complexes. The most significant antiproliferative activity was observed for C1 (IC50 = 0.69 µM, MAE = 73.96%) and C2 (IC50 = 3.78 µM, MAE = 60.35%) (where MAE represents the maximal antiproliferative effect) against A431 cell line. The mechanistic study evidenced the same pathway for the death of A431 cells treated with the complexes, although the results for C2 were obtained at approximately five times the concentration of C1. According to the study, both complexes induced cell cycle arrest in G2/M phase in A431 cells by upregulating the levels of p21, p27, p-cdc25C, and p-cdc2 and downregulating the levels of cdc25C, cdc2, and cyclin B1. In addition, apoptosis via a caspase-dependent mitochondrial pathway was confirmed by a decrease in Bcl-2 family proteins and an increase in the expression of procaspase-9 and 3. Also, the complexes induced autophagic cell death by activating the RAGE /PI3KC3/Beclin 1 pathway in A431 cells. DATA AVAILABILITY: CCDC 874052 and 874055 contain the supplementary crystallographic data for C1 and C2, respectively. These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/services/structures?pid=ccdc:874052,874055&sid=CCDCManual, or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223-336-033; or e-mail: deposit@ccdc.cam.ac.uk.

SnO2 nanoparticles: A recyclable and heterogeneous catalyst for Pechmann condensation of coumarins and Knoevenagel condensation-Michael addition of biscoumarins.

Recyclable SnO2 nanoparticles catalyze the Pechmann condensation between phenolic alcohols and ß-ketoesters at room temperature in ethanol leading to coumarins. Also, in another study the synthesis of biscoumarins catalyzed by SnO2 nanoparticles in the reaction between 4-hydroxycoumarin and aldehydes under same condition reactions. The corresponding coumarins and biscoumarins were produced efficiently with facility and excellent yields (93-98%). These approaches display the advantages of benign reaction conditions, non-chromatographic purification procedure, appropriate functional group tolerance and valuable process.

Cytotoxicity and mechanism of action of metal complexes: An overview.

After the discovery of cisplatin, many metal compounds were investigated for the therapy of diseases, especially cancer. The high therapeutic potential of metal-based compounds is related to the special properties of these compounds, such as their redox activity and ability to target vital biological sites. The overproduction of ROS and the consequent destruction of the membrane potential of mitochondria and/or the DNA helix is one of the known pathways leading to the induction of apoptosis by metal complexes. The apoptosis process can occur via the death receptor pathway and/or the mitochondrial pathway. The expression of Bcl2 proteins and the caspase family play critical roles in these pathways. In addition to apoptosis, autophagy is another process that regulates the suppression or promotion of various cancers through a dual action. On the other hand, the ability to interact with DNA is an important property found in several metal complexes with potent antiproliferative effects against cancer cells. These interactions were classified into two important categories: covalent/coordinated or subtle, and non-coordinated interactions. The anticancer activity of metal complexes is sometimes achieved by the simultaneous combination of several mechanisms. In this review, the anticancer effect of metal complexes is mechanistically discussed by different pathways, and some effective agents on their antiproliferative properties are explained.

Evaluation of central-metal effect on anticancer activity and mechanism of action of isostructural Cu(II) and Ni(II) complexes containing pyridine-2,6-dicarboxylate.

Two Cu(II) (C1) and Ni(II) (C2) complexes were designed through the one-pot reaction of pyridine-2,6-dicarboxylic acid and 2-aminobenzimidazole respectively with copper(II) nitrate hexahydrate and nickel(II) nitrate hexahydrate. Both complexes were characterized by single-crystal X-ray diffraction and the distorted octahedral geometry was recognized for them. The MTT assay indicated that the complexes have a significant antiproliferative effect on BEL-7404 cells. IC50 values confirmed that C1 (IC50 = 0.56 µM) is several times more potent than C2 (IC50 = 5.13 µM). The similar cellular uptake of the complexes in mentioned cells led to this proposal that the production of ROS with different values can be the main reason for different cytotoxicity of the complexes. In this study, C1 and C2 caused BEL-7404 cells arrest at the G2/M and S phases, respectively. The expression of p53, Bax up-regulation, and Bcl-2 down-regulation and also activation of procaspase-9, and 3 indicated that apoptosis through a caspase-dependent mitochondrion pathway is a remarkable pathway in BEL-7404 cells treated by C1 while mechanistic studies proved that C2 induce death of BEL-7404 cells through the activation of RAGE/PI3KC3/Beclin 1 autophagic cell signaling pathway, more specifically. The cytostatic effect of the complexes in the BEL-7404 3D spheroid model was depicted.

In Situ Formation of Copper Phosphate on Hydroxyapatite for Wastewater Treatment.

Here, we control the surface activity of hydroxyapatite (HAp) in wastewater treatment which undergoes peroxodisulfate (PDS) activation. Loading the catalytically active Cu species on HAp forms a copper phosphate in the outer layer of HAp. This modification turns a low active HAp into a high catalytically active catalyst in the dye degradation process. The optimal operational conditions were established to be [Cu-THAp]0 = 1 g/L, [RhB]0 = 20 mg/L, [PDS]0 = 7.5 mmol/L, and pH = 3. The experiments indicate that the simultaneous presence of Cu-THAp and PDS synergistically affect the degradation process. Additionally, chemical and structural characterizations proved the stability and effectiveness of Cu-THAp. Therefore, this work introduces a simple approach to water purification through green and sustainable HAp-based materials.

In silico analysis and in planta production of recombinant ccl21/IL1ß protein and characterization of its in vitro anti-tumor and immunogenic activity.

CCL21 has an essential role in anti-tumor immune activity. Epitopes of IL1ß have adjuvant activity without causing inflammatory responses. CCR7 and its ligands play a vital role in the immune balance; specifically, in transport of T lymphocytes and antigen-presenting cells such as dendritic cells to the lymph nodes. This study aimed to produce epitopes of CCL21 and IL1ß as a recombinant protein and characterize its in vitro anti-tumor and immunogenic activity. A codon-optimized ccl21/IL1ß gene was designed and synthesized from human genes. Stability and binding affinity of CCL21/IL1ß protein and CCR7 receptor were examined through in silico analyses. The construct was introduced into N. tabacum to produce this recombinant protein and the structure and function of CCL21/IL1ß were examined. Purified protein from transgenic leaves generated a strong signal in SDS PAGE and western blotting assays. FTIR measurement and MALDI-TOF/TOF mass spectrography showed that ccl21/IL-1ß was correctly expressed in tobacco plants. Potential activity of purified CCL21/IL1ß in stimulating the proliferation and migration of MCF7 cancer cell line was investigated using the wound healing method. The results demonstrated a decrease in survival rate and metastasization of cancer cells in the presence of CCL21/IL1ß, and IC50 of CCL21 on MCF7 cells was less than that of non-recombinant protein. Agarose assay on PBMCsCCR7+ showed that CCL21/IL1ß has biological activity and there is a distinguishable difference between chemokinetic (CCL21) and chemotactic (FBS) movements. Overall, the results suggest that CCL21/IL1ß could be considered an effective adjuvant in future in vivo and clinical tests.

Control of drug release from cotton fabric by nanofibrous mat.

A drug delivery system (DDSs) was developed in the present study based on textile substrates as drug carriers and electrospun nanofibers as a controller of release rate. Three types of drugs consisting of ciprofloxacin (CIP), clotrimazole (CLO), and benzalkonium chloride (BEN) were loaded into the cover glass (CG) and cotton fabrics (CF1 and CF2) separately. Then, the drug-loaded substrates were coated with polycaprolactone (PCL) and polycaprolactone/gelatin (PCL/Gel) nanofibers with various thicknesses. The morphology and hydrophilicity of the electrospun nanofibers and the release profile of drug-loaded samples were investigated. FTIR, XRD, and in vitro biodegradability analysis were analyzed to characterize the drug delivery system. A morphological study of electrospun fibers showed the mean diameter of the PCL and PCL/Gel nanofibers 127 ± 25 and 178 ± 38 nm, respectively. The drug delivery assay revealed that various factors affect the rate of drug releases, such as the type of drug, the type of drug carrier, and the thickness of the covered nanofibers. The study highlights the ability of drugs to load substrates with coated nanofibers as controlled drug delivery systems. In conclusion, it is shown that the obtained samples are excellent candidates for future wound dressing applications.

Advancements in Fabrication and Application of Chitosan Composites in Implants and Dentistry: A Review.

Chitosan is a biopolymer that is found in nature and is produced from chitin deacetylation. Chitosan has been studied thoroughly for multiple applications with an interdisciplinary approach. Antifungal antibacterial activities, mucoadhesion, non-toxicity, biodegradability, and biocompatibility are some of the unique characteristics of chitosan-based biomaterials. Moreover, chitosan is the only widely-used natural polysaccharide, and it is possible to chemically modify it for different applications and functions. In various fields, chitosan composite and compound manufacturing has acquired much interest in developing several promising products. Chitosan and its derivatives have gained attention universally in biomedical and pharmaceutical industries as a result of their desired characteristics. In the present mini-review, novel methods for preparing chitosan-containing materials for dental and implant engineering applications along with challenges and future perspectives are discussed.

Fibre-Reinforced Polymer Reinforced Concrete Members under Elevated Temperatures: A Review on Structural Performance.

Several experimental and numerical studies have been conducted to address the structural performance of FRP-reinforced/strengthened concrete structures under and after exposure to elevated temperatures. The present paper reviews over 100 research studies focused on the structural responses of different FRP-reinforced/strengthened concrete structures after exposure to elevated temperatures, ranging from ambient temperatures to flame. Different structural systems were considered, including FRP laminate bonded to concrete, FRP-reinforced concrete, FRP-wrapped concrete, and concrete-filled FRP tubes. According to the reported data, it is generally accepted that, in the case of insignificant resin in the post curing process, as the temperature increases, the ultimate strength, bond strength, and structure stiffness reduce, especially when the glass transition temperature Tg of the resin is approached and exceeded. However, in the case of post curing, resin appears to preserve its mechanical properties at high temperatures, which results in the appropriate structural performance of FRP-reinforced/strengthened members at high temperatures that are below the resin decomposition temperature Td. Given the research gaps, recommendations for future studies have been presented. The discussions, findings, and comparisons presented in this review paper will help designers and researchers to better understand the performance of concrete structures that are reinforced/strengthened with FRPs under elevated temperatures and consider appropriate approaches when designing such structures.

Sensitive and selective electrochemical detection of bisphenol A based on SBA-15 like Cu-PMO modified glassy carbon electrode.

This work reports the electrochemical detection of bisphenol A (BPA) using a novel and sensitive electrochemical sensor based on the Cu functionalized SBA-15 like periodic mesoporous organosilica-ionic liquid composite modified glassy carbon electrode (Cu@TU-PMO/IL/GCE). The structural morphology of Cu@TU-PMO is characterized by X-ray powder diffraction (XRD), energy dispersive X-ray analysis (EDX), Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), Field emission scanning electron microscopy (FE-SEM), and Brunauer-Emmett-Teller (BET). The catalytic activity of the modified electrode toward oxidation of BPA was interrogated with cyclic voltammetry (CV) and differential pulse voltammetry (DPV) in phosphate buffer solution (pH 7.0) using the fabricated sensor. The electrochemical detection of the analyte was carried out at a neutral pH and the scan rate studies revealed that the sensor was stable. Under the optimal conditions, a linear range from 5.0 nM to 2.0 µM and 4.0 to 500 µM for detecting BPA was observed with a detection limit of 1.5 nM (S/N = 3). The sensor was applied to detect BPA in tap and seawater samples, and the accuracy of the results was validated by high-performance liquid chromatography (HPLC). The proposed method provides a powerful tool for the rapid and sensitive detection of BPA in environmental samples.

Biosynthesis of AgNPs onto the urea-based periodic mesoporous organosilica (AgxNPs/Ur-PMO) for antibacterial and cell viability assay.

Nano-size silver particles were stabilized on the inner surfaces of urea based periodic mesoporous organosilica (Ur-PMO). Aqueous extract of Euphorbia leaves as a sustainable and green reducing agent was applied for Ag-nanoparticles growth into the Ur-PMO channels. Physical and chemical properties of organosilica materials synthesized using various techniques such as FT-IR, small-angle XRD, PXRD, FESEM, TEM, SEM-EDX and atomic absorption spectrometry (AAS) were examined. Finally, the AgNPs/Ur-PMO were investigated on cell viability assay. An in vitro cytotoxicity test using MMT assay displayed that the designed material has good biocompatibility and could be a promising candidate for biomedical applications. The results also showed that the AgNPs/Ur-PMO compounds (especially, PMO; 1.27% AgNPs) had relatively good antibacterial and antibiofilm effects. It seems that the use of these compounds in hospital environments can reduce nosocomial infections as well as reduce antibiotic-resistant bacteria.

3,5-Bis(trifluoromethyl) Phenylammonium triflate(BFPAT) as a Novel Organocatalyst for the Efficient Synthesis of 2,3-dihydroquinazolin-4(1H)-one Derivatives.

AIMS AND OBJECTIVES: A one-pot synthesis of 2,3-dihydroquinazolin-4(1H)-one derivatives by threecomponent cyclo-condensation of isatoic anhydride, aldehydes and amine or ammonium acetate has been developed using 3,5-Bis(trifluoromethyl) phenylammonium triflate (BFPAT) as a new organocatalyst. MATERIALS AND METHODS: All of the obtained products are known compounds and identified by IR, 1HNMR, 13CNMR and melting points. RESULTS: A wide variety of structurally different aldehydes reacted easily and rapidly to result in the relating 2,3-dihydroquinazolin-4(1H)-ones in good to excellent yield. CONCLUSION: We have demonstrated an extremely effective and new process for synthesizing 2,3- dihydroquinazolin-4(1H)-ones employing BFPAT as a novel organocatalyst in one-pot fashion.

Formation and stabilization of colloidal ultra-small palladium nanoparticles on diamine-modified Cr-MIL-101: Synergic boost to hydrogen production from formic acid.

Ultra-small nano-sized palladium particles were successfully stabilized within the pores of diamine groups grafted open metal site metal-organic frameworks of Cr-MIL-101; coordinated diamine groups of ethylene diamine (ED) and propyl diamine (PD) on the active site of chromium units of Cr-MIL-101. The physiochemical properties of the Pd@Cr-MOFs were investigated using FTIR, XRD, SEM/EDX mapping, TEM, BET, and AAS. The Cr-MIL-101 stabilized ultra-small Pd nanoparticles, Pd@(ethylene diamine)/Cr-MIL-101, and Pd@(propyl diamine)/Cr-MIL-101, displayed catalytic activity for clean dehydrogenation of formic acid and generation of hydrogen at room temperature. The resultant Pd@ED/Cr-MIL-101 catalyst indicates high catalytic activity with turnover frequency (TOF) of 583 h-1 at 328 K, which is superior to most of the reported catalysts, including Pd@PD/Cr-MIL-101 with TOF 532 h-1. Our studies open up a new method to the design of an ultra-small metal nanoparticle for the catalytic dehydrogenation of HCOOH.

Organocatalytic Combinatorial Synthesis of Quinazoline, Quinoxaline and Bis(indolyl)methanes.

AIMS AND OBJECTIVE: An efficient and practical procedure for the synthesis of heterocyclic compounds such as quinazolines, quinoxalines and bis(indolyl)methanes was developed using 3,5-bis(trifluoromethyl) phenyl ammonium hexafluorophosphate (BFPHP) as a novel organocatalyst. MATERIALS AND METHODS: All of the obtained products are known compounds and identified by IR, 1HNMR, 13CNMR and melting points. RESULT: Various products were obtained in good to excellent yields under reaction conditions. CONCLUSION: The BFPHP organocatalyst demonstrates a novel class of non-asymmetric organocatalysts, which has gained much attention in green chemistry.

Solvent-mediated Highly Efficient Synthesis of [1,2,4]triazolo/benzimidazoloquinazolinone Derivatives.

OBJECTIVE: An efficient and catalyst-free procedure for the synthesis of [1,2,4]triazolo/benzimidazolo quinazolinones has been developed in 2,2,2-trifluoroethanol or deep eutectic solvent(DESs) as a clean reaction media. METHODS: All of the obtained products are known compounds and identified by IR, 1HNMR,13CNMR, and melting points. RESULT: Various products were obtained in good to excellent yields under reaction conditions. CONCLUSION: We have efficiently developed a practical and catalyst-free approach for the synthesis of [1,2,4]triazolo/benzimidazolo quinazolinones employing TFE as a clean and reusable media.

Two-Step Macrocycle Synthesis by Classical Ugi Reaction.

The direct nonpeptidic macrocycle synthesis of α-isocyano-ω-amines via the classical Ugi four-component reaction (U-4CR) is introduced. Herein an efficient and flexible two-step procedure to complex macrocycles is reported. In the first step, the reaction between unprotected diamines and isocyanocarboxylic acids gives high diversity of unprecedented building blocks in high yield. In the next step, the α-isocyano-ω-amines undergo a U-4CR with high diversity of aldehydes and carboxylic acids in a one-pot procedure. This synthetic approach is short and efficient and leads to a wide range of macrocycles with different ring sizes.

Concise Synthesis of Macrocycles by Multicomponent Reactions.

A short reaction pathway was devised to synthesize a library of artificial 18-27-membered macrocycles. The five-step reaction sequence involves ring opening of a cyclic anhydride with a diamine, esterification, coupling with an amino acid isocyanide, saponification, and, finally, macro-ring closure using an Ugi or, alternatively, a Passerini multicomponent reaction. Three out of the five steps allow for the versatile introduction of linker elements, side chains, and substituents with aromatic, heteroaromatic, and aliphatic character. The versatile pathway is described for 15 different target macrocycles on a mmol scale. Artificial macrocycles have recently become of great interest due to their potential to bind to difficult post-genomic targets.