Lung Epithelial Carcinoma Cells Research Articles

Epigallocatechin-3-gallate Synergistically Inhibits the Proliferation of Lung Cancer Cells with Gemcitabine by Induction of Apoptosis Mediated by ROS Generation.

The present study focused on the formulation, characterization, and evaluation of solid lipid nanoparticles (SLNs) loaded with gemcitabine (GEM) and epigallocatechin-3-gallate (EGCG) for lung cancer treatment. A 2-level, 3-factor factorial design was used to optimize various process parameters in the preparation of SLNs. The average particle size and polydispersity index (PDI) of GEM-EGCG SLNs were found to be 122.8 ± 8.02 and 0.1738 ± 0.02, respectively. Drug loading and release studies indicated a sustained release behavior for GEM-EGCG SLNs, with release kinetics confirmed by the Higuchi model. Cell viability and anticancer activities were assessed using the MTT assay, which determined an IC50 value of 12.5 μg/mL for GEM-EGCG SLNs against A549 cell lines (lung carcinoma epithelial cells). The SLNs were able to internalize into the nuclei of cells, likely due to their small particle size, and were effective in killing cancer cells. Additionally, a study of ROS production-mediated apoptosis of A549 cells was performed through FACS. GEM-EGCG SLNs were found to be stable for 3 months. In vivo studies revealed better drug distribution in the lungs and improved pharmacokinetic profile compared with pure drugs. Overall, the results suggest that combining GEM and EGCG in biocompatible SLNs has resulted in synergistic antitumor potential and improved bioavailability for both drugs, making it a promising anticancer therapeutic regimen against lung cancer.

2D TiO2 Nanosheets Decorated Via Sphere-Like BiVO4: A Promising Non-Toxic Material for Liquid Phase Photocatalysis and Bacterial Eradication.

An in-depth investigation was conducted on a promising composite material (BiVO4/TiO2), focusing on its potential toxicity, photoinduced catalytic properties, as well as its antibiofilm and antimicrobial functionalities. The preparation process involved the synthesis of 2D TiO2 using the lyophilization method, which was subsequently functionalized with sphere-like BiVO4 through wet impregnation. Finally, we developed BiVO4/TiO2 S-scheme heterojunctions which can greatly promote the separation of electron-hole pairs to achieve high photocatalytic performance. The evaluation of concentration- and time-dependent viability inhibition was performed on human lung carcinoma epithelial A549 cells. This assessment included the estimation of glutathione levels and mitochondrial dehydrogenase activity. Significantly, the BiVO4/TiO2 composite demonstrated minimal toxicity towards A549 cells. Impressively, the BiVO4/TiO2 composite exhibited notable photocatalytic performance in the degradation of rhodamine B (k=0.135 min-1) and phenol (k=0.016 min-1). In terms of photoinduced antimicrobial performance, the composite effectively inactivated both gram-negative E. coli and gram-positive E. faecalis bacteria upon 60 minutes of UV-A light exposure, resulting in a significant log 6 (log 10 CFU/mL) reduction in bacterial count. In addition, a 49 % reduction of E. faecalis biofilm was observed. These promising results can be attributed to the unique 2D morphology of TiO2 modified by sphere-like BiVO4, leading to an increased generation of (intracellular) hydroxyl radicals, which plays a crucial role in the treatments of both organic pollutants and bacteria. This research has significant potential for various applications, particularly in addressing environmental contamination and microbial infections.

Human coronavirus OC43 infection remodels connexin 43-mediated gap junction intercellular communication in vitro.

β-coronaviruses cause acute infection in the upper respiratory tract, resulting in various symptoms and clinical manifestations. OC43 is a human β-coronavirus that induces mild clinical symptoms and can be safely studied in the BSL2 laboratory. Due to its low risk, OC43 can be a valuable and accessible model for understanding β-coronavirus pathogenesis. One potential target for limiting virus infectivity could be gap junction-mediated communication. This study aims to unveil the status of cell-to-cell communications through gap junctions in human β-coronavirus infection. Infection with OC43 leads to reduced expression of Cx43 in A549, a lung epithelial carcinoma cell line. Infection with this virus also shows a significant ER and oxidative stress increase. Internal localization of Cx43 is observed post-OC43 infection in the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) region, which impairs the gap junction communication between two adjacent cells, confirmed by Lucifer yellow dye transfer assay. It also affects hemichannel formation, as depicted by the EtBr uptake assay. Impairment of Cx43 trafficking and the ability to form hemichannels and functional GJIC are hampered by virus-induced Golgi apparatus disruption. Altogether, these results suggest that several physiological changes accompany OC43 infection in A549 cells and can be considered an appropriate model system for understanding the differences in gap junction communication post-viral infections. This model system can provide valuable insights for developing therapies against human β-coronavirus infections.IMPORTANCEThe enduring impact of the recent SARS-CoV-2 pandemic underscores the importance of studying human β-coronaviruses, advancing our preparedness for future coronavirus infections. As SARS-CoV-2 is highly infectious, another human β-coronavirus OC43 can be considered an experimental model. One of the crucial pathways that can be considered is gap junction communication, as it is vital for cellular homeostasis. Our study seeks to understand the changes in Cx43-mediated cell-to-cell communication during human β-coronavirus OC43 infection. In vitro studies showed downregulation of the gap junction protein Cx43 and upregulation of the endoplasmic reticulum and oxidative stress markers post-OC43 infection. Furthermore, HCoV-OC43 infection causes reduced Cx43 trafficking, causing impairment of functional hemichannel and GJIC formation by virus-mediated Golgi apparatus disruption. Overall, this study infers that OC43 infection reshapes intercellular communication, suggesting that this pathway may be a promising target for designing highly effective therapeutics against human coronaviruses by regulating Cx43 expression.

Apoptosis inducing anti-proliferative activity of Citrullus lanatus seeds against A549 cell lines

Cancer is a leading dangerous death-causing disease in millions over the world. It arises due to the uncontrolled growth of mal-functioned cells and formed as tumors. The disease can affect any part of the body. Still, it is a quest to find anti-cancer drugs which has been the major research endeavor around the globe. Traditionally humans use plants and their derived products as a source to cure various diseases. In recent years many researches had paved the way to use plant-based drugs. The current research aims to evaluate the anticancer activity of Citrullus lanatus seeds against A549 lung carcinoma epithelial cell lines. The study uses C. lanatus seeds which naturally contains antioxidants and phytochemicals that prevent cancer cell proliferation. The ethanolic seed extract of C. lanatus showed the presence of phytochemicals such as saponins, alkaloids, proteins and flavonoids by preliminary screening. The extract was tested for its anti-inflammatory showing 96.16 % at maximum concentration. The microbial assays also showed good signs of inhibition against the microorganisms by forming a zone of inhibition. The safety and efficacy of the extract were determined by MTT assay for the cytotoxicity using A549 cancer cell lines and non-cancerous cell lines. The IC50 concentration of C. lanatus seed extract showed dosage dependently at 51.73 μg/ml for A549 cell lines. They also resulted in significant induced cell cycle arrest and apoptosis at the G2 phase by inhibiting the A549 cell line proliferation. The present study works on lung carcinoma to find a better procurement in a traditional way that can develop future hope in the pharmaceutical industry.

Insights into the selective anticancer activity of [SnIV(L)(Cl)2(OH2)] [L =(E)-N,N-diethyl-2-(2-hydroxy-3-methoxybenzylidene)hydrazinecarbothioamide] at thiosemicarbazone appended tin(IV) site

We herein report the synthesis of a mononuclear tin(IV) complex [SnIV(L)(Cl)2(OH2)] [L = (E)-N,N-diethyl-2-(2-hydroxy-3-methoxybenzylidene)hydrazinecarbothioamide] (1). From the X-ray crystallographic characterization the molecular geometry of 1 around Sn(IV) center has been found to be distorted octahedron. The present report illustrates the selective reactivity of 1 against human lung carcinoma epithelial cell line, A549 by inducing depolarization of the mitochondrial membrane potential resulting in selective cancer cell death.

Anti-cancer drug-mediated increase in mitochondrial mass limits the application of metabolic viability-based MTT assay in cytotoxicity screening.

The high-throughput metabolic viability-based colorimetric MTT test is commonly employed to screen the cytotoxicity of different chemotherapeutic drugs. The assay assumes a cell density-dependent linear correlation with the MTT spectral absorbance. Therefore, the present study aimed to compare the cytotoxicity assessment between the MTT assay and gold standard cell number enumeration. The cytotoxicity was induced by Cisplatin, Etoposide, and Doxorubicin in human lung epithelial adenocarcinoma cells (A549) and cervix carcinoma (HeLa) cell lines. The mitochondrial mass was estimated, and immunoblotting of succinate dehydrogenase (SDH-A) was performed following drug treatment in both cell lines. Student's t-test paired analysis was employed to calculate the significance of the results, where the value p < 0.05 was considered statistically significant. The drug-induced cytotoxic response estimated by MTT absorbance did not show any significant difference with respect to control, and no correlation was observed with the enumerated cell number in both A549 and HeLa cells. Interestingly, per-cell metabolic viability was found to be increased by 1.18 to 3.26-fold (p < 0.05) following drug treatment. Further, mechanistic investigation revealed a drug concentration-dependent significant increase in mitochondrial mass (1.21 to 4.2-fold) and upregulation of SDH protein (50-70%) as well as enzymatic activity with respect to control in both A549 and Hela cells. The limitation of the MTT assay for drug-induced cytotoxicity assessment is due to increased mitochondrial mass and SDH upregulation in surviving cells, leading to enhanced formazan formation. This leads to a lack of correlation between cell number and MTT spectral absorbance, suggesting that the MTT assay may provide an erroneous conclusion for cytotoxicity assessment.

Comparative Studies of Resveratrol, Oxyresveratrol and Dihydrooxyresveratrol on Doxorubicin-Treated Lung Cancer Cells.

This research aims to comparatively investigate the capability of resveratrol (RES) and RES analogues, oxyresveratrol (Oxy-RES) and dihydrooxyresveratrol (DHoxy-RES), to potentiate doxorubicin (DOX) effects against lung carcinoma epithelial cells. All experiments were performed on lung carcinoma cell lines (A549) with DOX combination between DOX and RES or RES analogues. Cell viability or growth inhibitory effect was assessed by MTT assay and genes associated with survival and metastasis were monitored by real-time polymerase chain reaction (RT-PCR). DOX obviously demonstrated cytotoxic and anti-metastatic activities against A549 cells. Expression of gene-associated with both activities was potentiated by RES and RES analogues. Oxy-RES showed highest capability to potentiate DOX effects. DHoxy-RES showed nearly no effect to DOX activities. These results provided an important basis of DOX combination with RES analogues, especially Oxy-RES, for better therapeutic effect. Further studies in human should be performed on exploring combination of DOX and Oxy-RES.

Selective Modulation of the Human Glucocorticoid Receptor Compromises GR Chromatin Occupancy and Recruitment of p300/CBP and the Mediator Complex

Exogenous glucocorticoids are frequently used to treat inflammatory disorders and as adjuncts for the treatment of solid cancers. However, their use is associated with severe side effects and therapy resistance. Novel glucocorticoid receptor (GR) ligands with a patient-validated reduced side effect profile have not yet reached the clinic. GR is a member of the nuclear receptor family of transcription factors and heavily relies on interactions with coregulator proteins for its transcriptional activity. To elucidate the role of the GR interactome in the differential transcriptional activity of GR following treatment with the selective GR agonist and modulator dagrocorat compared to classic (ant)agonists, we generated comprehensive interactome maps by high-confidence proximity proteomics in lung epithelial carcinoma cells. We found that dagrocorat and the antagonist RU486 both reduced GR interaction with CREB-binding protein/p300 and the mediator complex compared to the full GR agonist dexamethasone. Chromatin immunoprecipitation assays revealed that these changes in GR interactome were accompanied by reduced GR chromatin occupancy with dagrocorat and RU486. Our data offer new insights into the role of differential coregulator recruitment in shaping ligand-specific GR-mediated transcriptional responses.

Nanoencapsulation of green tea catechin (−)-Epigallocatechin-3- Gallate (EGCG) in niosomes and assessment of its anticancer activity against lung cancer

Lung cancer is one of the leading causes of cancer-related deaths worldwide. In chemotherapy, the use of strong cytotoxic drugs and the specificity problems of these drugs also affect healthy cells and tissues. For this reason, the purpose of cancer treatment is to ensure that a suitable drug directly affects cancer cells at the appropriate dose. With nanotechnology, steps have been taken for an effective treatment that develops nano-transporters to deliver the drug molecule to the target cell in a specific, controlled manner. Another development is the discovery of theranostic agents used for both diagnostic and therapeutic purposes. In this study, a smart molecule was developed using the anticancer and antioxidant Epigallocatechin-3-Gallate (EGCG) molecule found in green tea, which is commonly consumed in our society. This molecule was encapsulated with niosomes to increase its stability and specificity. In this study, niosomes with an average size of 150 nm were synthesized using the thin film hydration technique. The zeta potential value of niosomes varied between −25 mV and −30 mV. Niosomes have been functionalized with indocyanine green (ICG) fluorescent dye and made suitable for optical imaging. The encapsulation efficiencies of the EGCG molecule and the ICG fluorescent dye were 10.1 % and 34.4 %, respectively. The release of EGCG from niosomes was an initial fast and then a slower release. 32 % of EGCG was released from niosomes within the first 3 h. Also, Cetuximab molecule was conjugated to niosomes with 75.8 % efficiency in order to provide lung cancer specificity and increase the anticancer effect. DLS, FTIR, XPS and TEM were used in the characterization phase of nanoparticles. While DLS and TEM provide information about dimensional analysis, FTIR and XPS were performed to verify the conjugations. Cytotoxicity, apoptosis, fluorescence imaging and incorporation studies of the molecule design created for theranostic purposes in A549 lung carcinoma and BEAS-2B normal bronchial epithelial cells were examined in vitro. As a result of these studies, it was determined that the synthesized molecule design has more involvement, toxic and apoptotic effects on A549 lung carcinoma cells. In this study, the therapeutic efficacy of the synthesized niosomal molecule design on the target cell and its potential to be used in cancer treatment were revealed and it is thought that it will contribute to the field of biotechnology.

Efficient Induction of Apoptosis in Lung Cancer Cells Using Bismuth Sulfide Nanoparticles.

The use of nanomaterial-based radiosensitizers to improve the therapeutic ratio has gained attraction in radiotherapy. Increased radiotoxicity applied to the tumor region may result in adverse impact on the unexposed normal cells to the radiation, a phenomenon known as radiation-induced bystander effect (RIBE). This study aimed to investigate the effect of Bi2S3@BSA nanoparticles (NPs) as radiosensitizers on the enhancement of bystander response in non-irradiated cells. Lung carcinoma epithelial cells were exposed to 6 MV x-ray photons at different doses of 2 and 8 Gy, with and without Bi2S3@BSA NPs. The irradiated-cell's conditioned medium (ICCM) was collected and incubated with MCR-5 human fetal lung fibroblasts. This study showed that ICCM collected from 2-Gy-irradiated A549 cells in the presence of Bi2S3@BSA NPs reduced the cell viability of MCR-5 bystander cells more than ICCM collected from irradiated cells without NPs (P<0.05), whereas such a difference was not observed after 8-Gy radiation. The mRNA expression of the BAX and XPA genes, as well as the cell death rate in MCR-5 bystander cells, revealed that the Bi2S3@BSA NPs significantly improved bystander response at 2-Gy (P<0.05), but the efficacy was not statistically significant after 8-Gy Irradiation. The results indicated that the presence of NPs did not affect bystander response enhancement at higher concentrations. These findings highlighted the potential use of radiation-enhancing agents and their benefits in radiotherapy techniques with high doses per fraction.

Nonthreaded Isomers of Sungsanpin and Ulleungdin Lasso Peptides Inhibit H1299 Cancer Cell Migration.

Lasso peptides are a structurally distinct class of biologically active natural products defined by their short sequences with impressively interlocked tertiary structures. Their characteristic peptide [1]rotaxane motif confers marked proteolytic and thermal resiliency, and reports on their diverse biological functions have been credited to their exceptional sequence variability. Because of these unique properties, taken together with improved technologies for their biosynthetic production, lasso peptides are emerging as a designable scaffold for peptide-based therapeutic discovery and development. Although the defined structure of lasso peptides is recognized for its remarkable properties, the role of the motif in imparting bioactivity is less understood. For example, sungsanpin and ulleungdin are natural lasso peptides that similarly exhibit encouraging cell migration inhibitory activities in A549 lung carcinoma epithelial cells, despite sharing only one-third of the sequence homology. We hypothesized that the shape of the lasso motif is beneficial for the preorganization of the conserved residues, which might be partially retained in variants lacking the threaded structure. Herein, we describe solid-phase peptide synthesis strategies to prepare acyclic, head-to-side chain (branched), and head-to-tail (macrocyclic) cyclic variants based on the sungsanpin (Sun) and ulleungdin (Uln) sequences. Proliferation assays and time-lapse cell motility imaging studies were used to evaluate the cell inhibitory properties of natural Sun compared with the synthetic Sun and Uln isomers. These studies demonstrate that the lasso motif is not a required feature to slow cancer cell migration and more generally show that these nonthreaded isomers can retain similar activity to the natural lasso peptide despite the differences in their overall structures.

Fabrication of α-mangostin – loaded liposomes for cytotoxic-activity against A549 lung-cancer spheroids

α-mangostin is a natural product isolated from the mangosteen pericarps with diverse biological activities, including cytotoxicity against cancer cells. However, the application of α-mangostin in cancer treatment is limited due to the high cytotoxicity and poor solubility in water. In this research, we fabricated α-mangostin-loaded liposomes from soybean lecithin and cholesterol to enhance the solubility in water of α-mangostin and reduce side effects in the treatment of cancer. The liposomal membrane uses Soybean Lecithin (SBL) as a phospholipid and Tocopherol (Toc) as a stabilizer, at 4 ratios of SBL/Toc are 1/1, 2/1, 4/1, 8/1. Experimental results showed that liposomes with SBL/Toc molar ratio of 4/1 had a mean size value of 105.8 ± 3.9 nm, and a polydispersity index (PDI) of 0.149. The encapsulation efficiency was 51.3 %. We believe that this formulation has the potential to be developed into an improved drug delivery system for α-mangostin. The lung carcinoma epithelial cells (A549) were cultured in microwell for 14 days to form spheroids. Then, spheroids were probed with a concentration of α-mangostin-loaded liposomes of 10 µM. The results showed the ability to significantly reduce cell viability after 36 hours of testing.

Effect of COVID-19 mRNA Vaccine on Human Lung Carcinoma Cells In Vitro by Means of Raman Spectroscopy and Imaging.

The effect of COVID-19 mRNA vaccine on human lung epithelial carcinoma cells (A549) in vitro as a convenient preclinical model was studied by means of Raman spectroscopy and imaging. The article focuses on Raman imaging as a tool to explore apoptosis and oxidative phosphorylation in mitochondrial dysfunctions. The Raman results demonstrate alterations in the oxidation-reduction pathways associated with cytochrome c. We found that the COVID-19 mRNA vaccine downregulates the concentration of cytochrome c upon incubation with tumorous lung cells. The concentration of the oxidized form of cytochrome c in the mitochondria of lung cells decreases upon incubation with the COVID-19 mRNA vaccine. A lower concentration of oxidized cytochrome c in mitochondria illustrates lower effectiveness of oxidative phosphorylation (respiration), reduced apoptosis, and lessened ATP production. Moreover, mRNA vaccine significantly increases de novo lipids synthesis in lipid droplets up to 96 h and alterations in biochemical composition. It seems that the lipid composition of cells returns to the normal level for a longer incubation time (14 days). In the cell nucleus, the mRNA vaccine does not produce statistically significant changes.

Long‐term and fast‐bactericidal activity of methacrylamide‐based copolymer for antibiofilm coatings and antibacterial wipes applications

AbstractBacterial‐related infections can be hazardous for human health and the surrounding environment. Traditional antibiotic‐based treatments for these infections are increasingly ineffective due to the emergence of antibiotic‐resistant bacteria. Antimicrobial peptide mimics have emerged as promising replacements owing to their potency against bacteria and lack of susceptibility to generate resistant cells. Thus, we synthesized a random copolymer, consisting of aminopropyl methacrylamide and benzyl methacrylamide (AB polymer) by random co‐polymerization that mimics host–defense antimicrobial peptides. For its use as a coating, the AB polymer is drop‐casted onto a cleaned glass substrate and tested for its antibacterial activity toward Escherichia coli and Staphylococcus aureus, wherein almost 99% of antibacterial activity was observed within 5 min. The prepared coating also possessed excellent longevity characteristics of up to 5 weeks. The AB polymer is also able to inhibit biofilm formation as well as disrupt a mature biofilm and can also be employed as an antibacterial wipe for cleaning bacterial contaminated surfaces. Mechanism study through SEM analysis showed that the AB polymer ruptures the bilayer membrane of both bacterial strains, thereby leading to pore formation causing cell death. Cell viability study depicted that 71% of the A549 lung carcinoma epithelial cells are viable compared to 80% on bare glass substrate. Thus, the synthesized AB polymer may be used in a variety of antibacterial applications directly in the form of solution (wipes) or forming a coating (drop casted/spray coated) for battling bacterial colonization.

On the Tunability of Toxicity for Viologen-Derivatives as Anolyte for Neutral Aqueous Organic Redox Flow Batteries.

Viologen-derivatives are the most widely used redox organic molecules for neutral pH negative electrolyte of redox flow batteries. However, the long-established toxicity of the herbicide methyl-viologen raises concern for deployment of viologen-derivatives at large scale in flow batteries. Herein, we demonstrate the radically different cytotoxicity and toxicology of a series of viologen-derivatives in in vitro assays using model organisms representative of human and environmental exposure, namely human lung carcinoma epithelial cell line (A549) and the yeast Saccharomyces cerevisiae. The results show that safe viologen derivatives can be molecularly engineered, representing a promising family of negolyte materials for neutral redox flow batteries.

Sodium pyruvate exerts protective effects against cigarette smoke extract-induced ferroptosis in alveolar and bronchial epithelial cells through the GPX4/Nrf2 axis

BackgroundFerroptosis in alveolar and bronchial epithelial cells is one of the main mechanisms underlying the development of chronic obstructive pulmonary disease (COPD). Sodium pyruvate (NaPyr) is a natural antioxidant in the body, exhibiting anti-inflammatory and antioxidant activities. NaPyr has been used in a Phase II clinical trial as a novel therapy for COPD; however, the mechanism underlying NaPyr-mediated therapeutic benefits in COPD is not well understood.ObjectiveWe aimed to assess the protective effects of NaPyr and elucidate its potential mechanism in cigarette smoke extract (CSE)-induced ferroptosis.To minic the inflammatory response and ferroptosis triggered by cigarette smoke in COPD in an invitro cell based system, we expose a human bronchial epithelial cells to CSE.MethodsTo minic the inflammatory response and ferroptosis triggered by cigarette smoke in COPD in an invitro cell based system, the A549 (human lung carcinoma epithelial cells) and BEAS-2B (bronchial epithelial cells) cell lines were cultured, followed by treatment with CSE. To measure cellular viability and iron levels, we determined the levels of malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS), mitochondrial superoxide (MitoSOX), membrane potential (MMP), and inflammatory factors (tumor necrosis factor [TNF] and interleukin [IL]-8), and examined CSE-induced pulmonary inflammation and ferroptosis. To clarify the molecular mechanisms of NaPyr in COPD therapy, we performed western blotting and real-time PCR (qPCR) to determine the expression of glutathione peroxidase 4 (GPX4), nuclear factor E2-related factor 2 (Nrf2), and cyclooxygenase 2 (COX2).ResultsWe found that NaPyr effectively mitigated CSE-induced apoptosis and improved apoptosis induced by erastin, a ferroptosis inducer. NaPyr significantly decreased iron and MDA levels and increased GSH levels in CSE-induced cells. Furthermore, NaPyr suppressed ferroptosis characteristics, such as decreased levels of ROS, MitoSOX, and MMP. NaPyr significantly increases the expression levels of GPX4 and Nrf2, indicating that activation of the GPX4/Nrf2 axis could inhibit ferroptosis in alveolar and bronchial epithelial cells. More importantly, NaPyr inhibited the secretion of downstream inflammatory factors, including TNF and IL-8, by decreasing COX2 expression levels to suppress CSE-induced inflammation.ConclusionAccordingly, NaPyr could mitigate CSE-induced ferroptosis in alveolar and bronchial epithelial cells by activating the GPX4/Nrf2 axis and decreasing COX2 expression levels. In addition, NaPyr reduced the secretion of inflammatory factors (TNF and IL-8), affording a novel therapeutic candidate for COPD.Graphical

Molecular docking and biological activities of Ni(II), Cu(II) and Co(II) complexes with a new potentially hexadentate polyamine ligand; X-ray crystal structure of the Cu(II) complex

Three new metal complexes have been obtained from the reaction of a new polyamine (L) with Ni(II), Cu(II), and Co(II) ions. The X-ray structural analysis of the Cu(II) complex shows that the copper atom is in a very distorted square pyramidal environment, coordinated by five of the six nitrogen donor atoms of the potentially hexadentate ligand. To evaluate the biological potential of the ligand and the synthesized metal complexes, their binding behavior with DNA was studied by molecular modeling methods. The Molecular docking studies showed that the free ligand and its complexes were bound to the major groove of DNA. The antioxidant activities of the ligand and its metal complexes were also assessed, in vitro, using 2,2-diphenyl-1-picrylhydrazyl. The synthesized compounds were tested for activity against lung carcinoma epithelial cells (A549) using the MTT cell viability assay. A comparative study of the IC50 values indicated that the Cu(II) complex exhibited the highest activity, while the Co(II) and Ni(II) complexes showed more potent antiproliferative activity than the ligand. The antibacterial activities of the synthesized complexes were evaluated using micro-broth dilution and disk diffusion methods. The complexes showed greater antibacterial activity than the free ligand. Communicated by Ramaswamy H. Sarma

Delicate Hybrid Laponite-Cyclic Poly(ethylene glycol) Nanoparticles as a Potential Drug Delivery System.

The objective of the study was to explore the feasibility of a new drug delivery system using laponite (LAP) and cyclic poly(ethylene glycol) (cPEG). Variously shaped and flexible hybrid nanocrystals were made by both the covalent and physical attachment of chemically homogeneous cyclized PEG to laponite nanodisc plates. The size of the resulting, nearly spherical particles ranged from 1 to 1.5 µm, while PEGylation with linear methoxy poly (ethylene glycol) (mPEG) resulted in fragile sheets of different shapes and sizes. When infused with 10% doxorubicin (DOX), a drug commonly used in the treatment of various cancers, the LAP-cPEG/DOX formulation was transparent and maintained liquid-like homogeneity without delamination, and the drug loading efficiency of the LAP-cPEG nano system was found to be higher than that of the laponite-poly(ethylene glycol) LAP-mPEG system. Furthermore, the LAP-cPEG/DOX formulation showed relative stability in phosphate-buffered saline (PBS) with only 15% of the drug released. However, in the presence of human plasma, about 90% of the drug was released continuously over a period of 24 h for the LAP-cPEG/DOX, while the LAP-mPEG/DOX formulation released 90% of DOX in a 6 h burst. The results of the cell viability assay indicated that the LAP-cPEG/DOX formulation could effectively inhibit the proliferation of A549 lung carcinoma epithelial cells. With the DOX concentration in the range of 1-2 µM in the LAP-cPEG/DOX formulation, enhanced drug effects in both A549 lung carcinoma epithelial cells and primary lung epithelial cells were observed compared to LAP-mPEG/DOX. The unique properties and effects of cPEG nanoparticles provide a potentially better drug delivery system and generate interest for further targeting studies and applications.

Isolation and Biological Activity of Iezoside and Iezoside B, SERCA Inhibitors from Floridian Marine Cyanobacteria.

Marine cyanobacteria are a rich source of bioactive natural products. Here, we report the isolation and structure elucidation of the previously reported iezoside (1) and its C-31 O-demethyl analogue, iezoside B (2), from a cyanobacterial assemblage collected at Loggerhead Key in the Dry Tortugas, Florida. The two compounds have a unique skeleton comprised of a peptide, a polyketide and a modified sugar unit. The compounds were tested for cytotoxicity and effects on intracellular calcium. Both compounds exhibited cytotoxic activity with an IC50 of 1.5 and 3.0 μΜ, respectively, against A549 lung carcinoma epithelial cells and 1.0 and 2.4 μΜ against HeLa cervical cancer cells, respectively. In the same cell lines, compounds 1 and 2 show an increase in cytosolic calcium with approximate EC50 values of 0.3 and 0.6 μΜ in A549 cells and 0.1 and 0.5 μΜ, respectively, in HeLa cells, near the IC50 for cell viability, suggesting that the increase in cytosolic calcium is functionally related to the cytotoxicity of the compounds and consistent with their activity as SERCA (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase) inhibitors. The structure-activity relationship provides evidence that structural changes in the sugar unit may be tolerated, and the activity is tunable. This finding has implications for future analogue synthesis and target interaction studies.

Imidazopyridine chalcones as potent anticancer agents: Synthesis, single-crystal X-ray, docking, DFT and SAR studies.

New imidazopyridine-chalcone analogs were synthesized through the Claisen-Schmidt condensation reaction. The newly synthesized imidazopyridine-chalcones (S1-S12) were characterized using spectroscopic and elemental analysis. The structures of compounds S2 and S5 were confirmed by X-ray crystallography. The global chemical reactivity descriptor parameter was calculated using theoretically (DFT-B3LYP-3-211, G) estimated highest occupied molecular orbital and lowest unoccupied molecular orbital values and the results are discussed. Compounds S1-S12 were screened on A-549 (lung carcinoma epithelial cells) and MDA-MB-231 (M.D. Anderson-Metastatic Breast 231) cancer cell lines. Compounds S6 and S12 displayed exceptional antiproliferative activity against lung A-549 cancer cells with IC50 values of 4.22 and 6.89 µM, respectively, compared to the standard drug doxorubicin (IC50 = 3.79 μM). In the case of the MDA-MB-231 cell line, S1 and S6 exhibited exceptionally superior antiproliferative activity with IC50 of 5.22 and 6.50 μM, respectively, compared to doxorubicin (IC50 = 5.48 μM). S1 was found to be more active than doxorubicin. Compounds S1-S12 were tested for their cytotoxicity on human embryonic kidney 293 cells, which confirmed the nontoxic nature of the active compounds. Further molecular docking studies verified that compounds S1-S12 have a higher docking score and interacted well with the target protein. The most active compound S1 interacted well with the target protein carbonic anhydrase II in complex with pyrimidine-based inhibitor, and S6 with human Topo IIα ATPase/AMP-PNP. The results suggest that imidazopyridine-chalcone analogs may serve as new leads as anticancer agents.