Human Lung Carcinoma Cells Research Articles

Toxicity evaluation of choline ionic liquid-based nanocarriers of pharmaceutical agents for lung treatment.

In vitro cytotoxicity evaluation of linear copolymer (LC) containing choline ionic liquid units and its conjugates with an antibacterial drug in anionic form, that is, p-aminosalicylate (LC_PAS), clavulanate (LC_CLV), or piperacillin (LC_PIP) was carried out. These systems were tested against normal: human bronchial epithelial cells (BEAS-2B), and cancers: adenocarcinoma human alveolar basal epithelial cells (A549), and human non-small cell lung carcinoma cell line (H1299). Cells viability, after linear copolymer LC and their conjugates addition for 72 h, was measured at concentration range of 3.125-100 μg/mL. The MTT test allowed the designation of IC50 index, which was higher for BEAS-2B, and significantly lower in the case of cancer cell lines. The cytometric analyzes, that is, Annexin-V FITC apoptosis assay and cell cycle analysis as well as gene expression measurements for interleukins IL6 and IL8 were carried out, and showed pro-inflammatory activity of tested compounds toward cancer cells, while it was not observed against normal cell line.

The system of self-consistent models based on quasi-SMILES as a tool to predict the potential of nano-inhibitors of human lung carcinoma cell line A549 for different experimental conditions

The different features of the impact of nanoparticles on cells, such as the structure of the core, presence/absence of doping, quality of surface, diameter, and dose, were used to define quasi-SMILES, a line of symbols encoded the above physicochemical features of the impact of nanoparticles. The correlation weight for each code in the quasi-SMILES has been calculated by the Monte Carlo method. The descriptor, which is the sum of the correlation weights, is the basis for a one-variable model of the biological activity of nano-inhibitors of human lung carcinoma cell line A549. The system of models obtained by the above scheme was checked on the self-consistence, i.e., reproducing the statistical quality of these models observed for different distributions of available nanomaterials into the training and validation sets. The computational experiments confirm the excellent potential of the approach as a tool to predict the impact of nanomaterials under different experimental conditions. In conclusion, our model is a self-consistent model system that provides a user to assess the reliability of the statistical quality of the used approach.

Novel Silver Complexes Based on Phosphanes and Ester Derivatives of Bis(pyrazol-1-yl)acetate Ligands Targeting TrxR: New Promising Chemotherapeutic Tools Relevant to SCLC Management

Bis(pyrazol-1-yl)acetic acid (HC(pz)2COOH) and bis(3,5-dimethyl-pyrazol-1-yl)acetic acid (HC(pzMe2)2COOH) were converted into the methyl ester derivatives 1 (LOMe) and 2 (L2OMe), respectively, and were used for the preparation of silver(I) complexes 3-5. The Ag(I) complexes were prepared by the reaction of AgNO3 and 1,3,5-triaza-7-phosphaadamantane (PTA) or triphenylphosphine (PPh3) with LOMe and L2OMe in methanol solution. All Ag(I) complexes showed a significant in vitro antitumor activity, proving to be more effective than the reference drug cisplatin in the in-house human cancer cell line panel containing examples of different solid tumors. Compounds were particularly effective against the highly aggressive and intrinsically resistant human small-cell lung carcinoma (SCLC) cells, either in 2D and 3D cancer cell models. Mechanistic studies revealed their ability to accumulate into cancer cells and to selectively target Thioredoxin (TrxR), thus leading to redox homeostasis unbalance and ultimately inducing cancer cell death through apoptosis.

Improvement of Proton Irradiation Effectiveness of Human Lung Carcinoma Cells A 549 in the Presence of Gold Nanoparticles

Purpose: To study was to study the effect of GNP nanoparticles on tumor cells of human lung carcinoma A 549 when irradiated with protons.
 Materials and methods:
 Cell culture: Human lung carcinoma cells A 549.
 Gold nanoparticles Au/PEG 6000/W 200/30 nm: A colloidal solution of gold nanoparticles purchased from the firm M 9 Nanomaterials & Technologies was used in the work.
 Proton irradiation: The irradiation of cells was carried out on a therapeutic proton beam in the Medical and Technical Complex of the Laboratory of Nuclear Problems Joint Institute for Nuclear Research.
 Determination of radiosensitivity of cells: By determining the clonogenic survival of cells.
 Determination of the genotoxic activity of nanoparticles under the action of proton irradiation: investigated using a micronucleus test with blocking cytokinesis. The genotoxicity of gold nanoparticles was estimated by the number of micronuclei per 1000 binuclear cells. Micronucleus were counted only in binuclear cells. At least 1000 binuclear cells were calculated for each dose, experiments were carried out in three repeats.
 Results: The frequency of micronucleus formation indicates an increase in the genotoxic effect of nanoparticles when irradiated with protons at a dose of 2 Gy. Proton irradiation caused an increase in the frequency of micronucleus formation depending on the concentration of nanoparticles. When irradiated with protons at a dose of 2 Gy in the presence and absence of nanoparticles, the difference in the frequency of micronucleus formation for the concentration of nanoparticles was 2.5 mg/ml – 1.1; for 5 mg/ml and 10 mg/ml – 1.2; for 15 mg/ml – 1.3 and for 30 mg/ml –1.5. Cell survival curves reflect a decrease in their survival rate when metal nanoparticles with high Z are added, which reflects the occurrence of radiosensitization effects. The gain for 10 % and 50 % survival rates is 1.4 and 2.5, respectively.
 Conclusions: Under the influence of proton irradiation, the genotoxic activity of gold nanoparticles in human lung carcinoma cells A 549 increases, depending on their concentration. The survival rate of human lung carcinoma A 549 cells irradiated with protons in the presence of gold nanoparticles decreases.

Exploring the Biological Properties of Zn(II) Bisthiosemicarbazone Helicates.

The design of artificial helicoidal molecules derived from metal ions with biological properties is one of the objectives within metallosupramolecular chemistry. Herein, we report three zinc helicates derived from a family of bisthiosemicarbazone ligands with different terminal groups, Zn2(LMe)2∙2H2O 1, Zn2(LPh)2∙2H2O 2 and Zn2(LPhNO2)23, obtained by an electrochemical methodology. These helicates have been fully characterized by different techniques, including X-ray diffraction. Biological studies of the zinc(II) helicates such as toxicity assays with erythrocytes and interaction studies with proteins and oligonucleotides were performed, demonstrating in all cases low toxicity and an absence of covalent interaction with the proteins and oligonucleotides. The in vitro cytotoxicity of the helicates was tested against MCF-7 (human breast carcinoma), A2780 (human ovarian carcinoma cells), NCI-H460 (human lung carcinoma cells) and MRC-5 (normal human lung fibroblasts), comparing the IC50 values with cisplatin. We will try to demonstrate if the terminal substituent of the ligand precursor exerts any effect in toxicity or in the antitumor activity of the zinc helicates.

Hydroponic Ginseng ROOT Mediated with CMC Polymer-Coated Zinc Oxide Nanoparticles for Cellular Apoptosis via Downregulation of BCL-2 Gene Expression in A549 Lung Cancer Cell Line

The unique and tailorable physicochemical features of zinc oxide nanoparticles (ZnO-NPs) synthesized from green sources make them attractive for use in cancer treatment. Hydroponic-cultured ginseng-root-synthesized ZnO-NPs (HGRCm-ZnO NPs) were coated with O-carboxymethyl chitosan (CMC) polymer, which stabilized and enhanced the biological efficacy of the nanoparticles. Nanoparticles were characterized by X-ray diffraction (XRD), UV-Vis spectroscopy, transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FT-IR), and energy-dispersive X-ray spectroscopy (EDS). The flower-shaped nanoparticles were crystalline in nature with a particle size of 28 nm. To evaluate if these NPs had anti-lung cancer activity, analysis was performed on a human lung carcinoma cell line (A549). HGRCm-ZnO nanoparticles showed less toxicity to normal keratinocytes (HaCaTs), at concentrations up to 20 µg/mL, than A549 cancer cells. Additionally, these NPs showed dose-dependent colony formation and cell migration inhibition ability, which makes them more promising for lung cancer treatment. Additionally, Hoechst and propidium iodide dye staining also confirmed that the NP formulation had apoptotic activity in cancer cells. Further, to evaluate the mechanism of cancer cell death via checking the gene expression, HGRCm ZnO NPs upregulated the BAX and Caspase 3 and 9 expression levels but downregulated Bcl-2 expression, indicating that the nanoformulation induced mitochondrial-mediated apoptosis. Moreover, these preliminary results suggest that HGRCm ZnO NPs can be a potential candidate for future lung cancer treatment.

Cytotoxic and antioxidant activities and phytochemical analysis of Smilax excelsa L. and Aegopodiumpodagraria L.

New curative and preventative approaches with high therapeutic efficacy and minimal side effects are needed for many forms of cancer. Therefore, the current study aimed to assess the cytotoxic and antioxidant capacity of Smilax excelsa and Aegopodium podagraria, which are consumed on a daily diet in the Black Sea region of Turkiye, as well as their phytochemical composition to pinpoint the compounds responsible for these activities. The effects of the treatments on human prostate (PC3), colorectal (HCT116), and lung (A549) carcinoma cell survival and free radical scavenging potentials were investigated. Total phenolic and flavonoid contents and significant phenolic compounds were detected and quantified by HPLC. The extracts reduced cell viability in all cancer cells in a dose-dependent manner, while the most potent cytotoxic effects were noted on PC3 cells. S. excelsa inhibited cell growth on PC3 cells at both lower and higher concentrations (50–1000 μg/mL) compared with the control (p < 0.05). S. excelsa methanol extract exhibited the strongest ABTS and DPPH free radical scavenging capacities, with the IC50 values of 17.16 and 45.81 μg/mL, respectively. The highest amounts of total phenolics and flavonoids, as well as chlorogenic acid and caffeic acid, were also observed in S. excelsa methanol extract. Our results suggest that S. excelsa and A. podagraria, along with the isolated compounds, may contribute to the treatment of prostate cancer. To the best of our knowledge, this is the first study analyzing the impacts of these plants on PC3, HCT116, and A549 cells.

Synthesis, crystal structure and evaluation of anticancer activities of some novel heterocyclic compounds based on thymol

A series of novel 1,3,4-thiadiazole, 1,3-thiazole and 1,3-thiazolidin-4-one derivatives bearing thymol were synthesized via cyclization of the corresponding thiosemicarbazones with acetic anhydride, ethyl bromoacetate, dimethyl acetylene dicarboxylate and phenacyl bromides. The structures of the newly synthesized compounds have been confirmed by IR, 1H NMR, 13C NMR, HRMS and single crystal X-ray diffraction analyses. All new thiosemicarbazones and their heterocyclic derivatives were evaluated for their in vitro cytotoxicity against four selected human cancer cell lines, namely, breast adenocarcinoma (MCF-7, MDA-MB- 231), lung carcinoma (A-549) and fibrosarcoma (HT-1080) cell line and compared with reference drug doxorubicine. The data illustrate that most target compounds show moderate to high cytotoxicity activities against the four human cancer cell lines. Especially, thiosemicarbazones 4b showed significant cytotoxicity on HT-1080 and A-549 cancer cell line with an IC50 values of 7.10 ± 0.32 and 14.40 ± 0.36 µM, respectively. Notably, induction of apoptosis by the compound 4b on HT-1080 and A-549 cells was evaluated using different staining techniques such as annexin V-FITC/PI. Moreover, flow-cytometric analysis also revealed that compound 4b caused arrest at the G2/M phase of the cell cycle and caspase-dependent apoptosis in HT-1080 and A-549 cells.

Effects of Apis dorsata Honey on the mRNA Expression of Selected CYP450, Pro-apoptotic, and Anti-apoptotic Genes during Induced Cytotoxicity in Cyclophosphamide-treated Human Lung Carcinoma (A549) Cells

Effects of Apis dorsata Honey on the mRNA Expression of Selected CYP450, Pro-apoptotic, and Anti-apoptotic Genes during Induced Cytotoxicity in Cyclophosphamide-treated Human Lung Carcinoma (A549) Cells

THE EXPRESSION OF TLR4, IFN-γ, TGF-β AND TNF-αLL LINE OF HUMAN SMALL CELL LUNG CARCINOMA NCI-H69 AND IN CISPLATIN-RESISTANT SUBLINE NCI-H69/CPR

Aim: to investigate the effect of teichoic acid Staphylococcus aureus for expression of pro-inflammatory cytokines and of TLR4 in a human small cell lung carcinoma cell line NCI-H69, and cisplatin resistant subline NCI-H69/CPR. Methods. Incubation of cells with teichoic acid (1 ng/m) conducted for 2 days. Expression level of TLR4, TGF-β, INF-γ, TNF-α was evaluated by the real time PCR on 7500 Real-Time PCR System, using specific primers and fluorochrome SYBR Green. The reverse transcription reaction was performed with High-Capacity cDNA Reverse Transcription Kit carried out under the conditions: 25 °C - 10 min, 37 °C ‒ 120 min and 85 °C ‒ 5 min. Results. In cell line culture NCI-H69 addition of teichoic acid increased expression of TLR4 by 1.3 times, and IFN-γ – by 1,1 times. Expression of TGF-β and TNF-α was decreased 2.5 and 4.9 times respectively. In cell line culture NCI-H69/CPR the addition of teichoic acid inhibited the expression of all studied parameters. Expression TLR4 decreased by 4.2 times, IFN-γ – by 1.4 times. Expression TGF-β and TNF-α was depressed 1.6 and 1.2 times. The presented data indicate that teichoic acid of bacterial origin provided the effect of modulating the inflammatory effect in lung cancer cell culture, sensitive and resistant to cisplatin. Conclusions. Teichoic acid as a ligand of TLR4 modulates the expression of pro-inflammatory and anti-inflammatory cytokines in small cell lung cancer cell culture and suppresses the expression of TLR4 and all investigated cytokines in the cisplatin-resistant cell line NCI-H69.

Luminescent cyclometalated platinum compounds with N, P, and O^O ligands: Density‐functional theory studies and analysis of the anticancer potential

Luminescent platinum cyclometalated complexes are species of interest mainly due to their applications in the optoelectronic and biological fields, especially with regard to their anticancer activity. Given this level of interest, a series of cyclometalated (2‐[2′‐thienyl]pyridinate, thpy and 2‐[2,4‐difluorophenyl]pyridinate, dfppy) platinum complexes with N‐donor, PTA (1,3,5‐triaza‐7‐phosphaadamantane) or chrysin‐derived ligands (incorporating piperidine, HL1, or morpholine, HL2, fragments) were synthesized. The complexes are luminescent with tunable emission wavelengths. Aggregation in solution was observed for [Pt(dfppy)L1], 5. Density‐functional theory (DFT) studies provided descriptions of the highest occupied molecular orbital (HOMO) and least unoccupied molecular orbital (LUMO) characteristics and their influence on the photophysical properties. The orbitals of 5–6 were different in nature to those of 1–4. Time‐dependent DFT (TD‐DFT) calculations showed that for 1–4 the excited states S1 and T1 reflect metal‐to‐ligand charge transfer (MLCT) and ligand‐centered (LC) (C^N) contributions while for 5–6 these states are an LC transition centered on L1 or L2. The speciation in DMSO and DMSO/H2O was evaluated. Biological studies showed that [Pt(thpy)Cl(Hthpy)], 1, [Pt(dfppy)Cl(Hdfppy)], 2, and 5 exert significant cytotoxic activity against human cervical (HeLa) and lung (A549) carcinoma cells. The cytotoxicity of 1 increased 2.84‐fold upon irradiation (blue). Microscopy assays on 5 showed that this compound accumulates in cytoplasmic organelles, preferentially in mitochondria. Mitochondrial metabolism was disrupted by the activity of the complexes, leading to a decline in the adenosine triphosphate (ATP) cellular content. Overall, the results show an alternative anticancer activity for complexes 1, 2, and 5, which could be of great interest for the treatment of tumors with acquired resistance to conventional DNA‐targeted anticancer drugs.

Synthesis, anticancer evaluation, and molecular docking studies of thiazolyl-pyrazoline derivatives

The molecular hybridization of thiazole and pyrazoline heterocyclic structures with diverse activities appears to be an interesting strategy for developing new anticancer compounds. This study presents the synthesis of eleven new thiazolyl-pyrazoline derivatives (7a-k) and the evaluation of their in-vitro anti-proliferative activities against human lung carcinoma (A549) and human melanoma cancer (A375) cell lines through MTT assay. In comparison to the positive reference drug erlotinib (IC50 = 34.16 µM in A549 and IC50 = 25.85 µM in A375), four compounds (7e, 7h, 7j, and 7k) were identified as the most active against both cell lines (especially compound 7k with IC50 = 20.28 µM in A549 and 16.08 µM in A375). Additionally, these potent compounds were selected to be investigated for their anti-metastasis and anti-inflammatory properties via inhibition of the expression of matrix metalloproteinase 2, 9 (MMP-2, 9) and cyclooxygenase 2 (COX-2). In A549 cells, upon exposure to compounds 7e and 7j, COX-2 expression is decreased, whereas compounds 7e, 7j, and 7k reduced COX-2 expression in A375 cell lines. Molecular docking studies were carried out to show the possible interactions of synthesized compounds with the predicted active site of the COX-2 protein. The results revealed that compounds 7e and 7j can bind well to the active site of COX-2 protein. Collectively, compounds 7e, 7j, and 7k are all promising candidates for further research towards the development of novel anticancer agents.

Arsenic trioxide promotes ERK1/2-mediated phosphorylation and degradation of BIMEL to attenuate apoptosis in BEAS-2B cells

Inorganic arsenic is highly toxic, widely distributed in the human environment and may result in multisystem diseases and several types of cancers. The BCL-2-interacting mediator of cell death protein (BIM) is a key modulator of the intrinsic apoptosis pathway. Interestingly, in the present study, we found that arsenic trioxide (As2O3) decreased BIMEL levels in human bronchial epithelial cell line BEAS-2B and increased BIMEL levels in human lung carcinoma cell line A549 and mouse Sertoli cell line TM4. Mechanismly, the 26S proteasome inhibitors MG132 and bortezomib could effectively inhibit BIMEL degradation induced by As2O3 in BEAS-2B cells. As2O3 activated extracellular signal-regulated kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) signaling pathways, but only the ERK1/2 MAPK inhibitor PD98059 blocked BIMEL degradation induced by As2O3. Furthermore, As2O3 induced-phosphorylation of BIMEL at multiple sites was inhibited by ERK1/2 MAPK inhibitor PD98059. Inhibition of As2O3-induced ERK1/2 MAPK phosphorylation increased the levels of BIMEL and cleaved-caspase-3 proteins and decreased BEAS-2B cell viability. As2O3 also markedly mitigated tunicamycin-induced apoptosis of BEAS-2B cells by increasing ERK1/2 phosphorylation and BIMEL degradation. Our results suggest that As2O3-induced activation of the ERK1/2 MAPK pathway increases phosphorylation of BIMEL and promotes BIMEL degradation, thereby alleviating the role of apoptosis in As2O3-induced cell death. This study provides new insights into how to maintain the survival of BEAS-2B cells before malignant transformation induced by high doses of As2O3.

Antioxidant and anticancer activities of Annona muricata L. and Antidesma bunius L. leaves, and molecular networking analysis using LC-MS/MS metabolomics

Several natural products are known to have anticancer activity, which helps prevent cancer. This study explores the potential use of different extracts of Annona muricata L. and Antidesma bunius L. leaves as an anticancer drug by testing its anti-oxidative and anticancer properties. Furthermore, metabolomics of these plant extracts was performed to characterize them. This project studied the bioactivities and phytochemistry of plants found in Mt. Makiling, Philippines. Hexane, ethyl acetate, and methanol leaf extracts of Annona muricata L. (Guyabano) and Antidesma bunius L. (Bignay) were screened for their anticancer and antioxidant properties. Extracts of each plant species were subjected to a clean-up procedure (removal of tannins and chlorophyll) and were analyzed using the same tests as the crude. The growth inhibitory effect against A-549 human lung carcinoma cells was determined using MTT assay, while the total antioxidant activity was determined using DPPH assay. All extracts exhibited both anticancer and antioxidant activity of varying degrees. Ethyl acetate crude extract of Annona muricata L. showed the highest percent growth inhibition against lung cancer cells, while methanol crude extract of Antidesma bunius L. showed the highest total antioxidant activity. The effect of the clean-up procedure varied per extract; some exhibited an enhanced activity while others exhibited a decreased activity upon clean-up. The extracts’ responses to free radicals and lung cancer cells can be attributed to phytochemicals like alkaloids, indoles, and phenols identified using qualitative phytochemical tests and LC-MS/MS analysis. Results suggest that Annona muricata L. and Antidesma bunius L. leaf extracts are potential anticancer and antioxidant agents.

Electrospun silk fibroin and gelatin blended nanofibers functionalized with noble metal nanoparticles for enhanced biomedical applications

The combination of highly anticancer active platinum group metals and biocompatible natural fibers exhibits significant anticancer activity while also allowing cell regeneration and repair to the damaged region. In this research, platinum and palladium nanoparticles anchored silk fibroin and gelatin (SF/GL/Pd-Pt) hybrid composite nanofiber was fabricated through the electrospinning method. The amino groups in SF and GL act as a reducingd stabilizing agent for the resulting Pd and Pt nanoparticles. Morphological and functional studies confirmed that crystalline Pd and Pt nanoparticles with average sizes of 5.11 and 3.03 nm are anchored on a 154.93 ± 34.19 nm SF/GL nanofiber matrix. The atomic force microscopic (AFM) images show that the SF/GL/Pd-Pt composite nanofiber has a thickness of 4.74 nm and a roughness area (Ra) of 258.5 nm. X-ray photoelectron spectroscopic (XPS) results confirmed the presence of C, N, O, Pt, and Pd in the composite fiber with an atomic percentage of 67.56%, 11.05%, 17.72%, 2.01% and 1.66%. respectively. This SF/GL/Pd-Pt composite nanofiber is more effective than its counterparts in terms of anticancer activity (IC50 value of 28.82 µg/mL−1) against A549 human lung carcinoma cells. Furthermore, the β-actin and Hsp90 gene expression in A549 cells confirmed its superior anticancer activity.

Insights into PLGA-encapsulated epigallocatechin 3-gallate nanoparticles as a new potential biomedical system: A computational and experimental approach

Biodegradable poly-lactic poly-glycolic copolymer (PLGA) represents one of the best strategies adopted to convey small molecules unstable and characterised by a low bioavailability if administered without vehicles. This is the case of Epigallocatechin-3-gallate (EGCG), which is one of the most interesting polyphenols from a biomedical point of view. In this study, the impact of EGCG on PLGA nanoparticles (NPs) properties has been studied underlining the role of the binary PVA/Poloxamer-407 as stabilizer system for obtaining colloidal stable NPs. Characterization has been carried out by dynamic light scattering (DLS), encapsulation efficiency, drug release studies, scanning electron microscopy (SEM) and infrared spectroscopy (IR). Molecular dynamics (MD) simulations have been used to model the PLGA and EGCG systems to understand the behaviour of NPs and the interactions that guided the EGCG encapsulation. The nanodispersions exhibited promising cytotoxic potentials in human lung carcinoma A549 cell lines enhancing the well-known growth inhibitor effect of the free EGCG.

Benzoate group attachment to TEMPO provides enhanced discrimination of liposomes fabricated using human lung normal and carcinoma cells

It is widely accepted that the lipid compositions of the plasma membranes of healthy and cancer cells significantly differ from each other. During the cancer progression, cancer cells change the lipid constituent of the membranes resulting in the loss of lipid asymmetry between the membrane leaflets. Consequently, physicochemical properties of the cell membranes are also changed in response to altered lipid organization. Partitioning of the spin probe 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) into the membranes of the cells has broadly been applied to characterize membrane properties of various cells in health and disease conditions. In this work, we used liposomes fabricated using lipids extracted from normal and carcinoma cells. This system permits the determination of the properties of the healthy and cancer cell membranes provided exclusively by its lipid components. Application of TEMPO-benzoate, in which the benzoate group is attached to the TEMPO, indicates significantly enhanced discrimination of liposomes between cancer and normal cells. Partitioning experiments with TEMPO-benzoate revealed relatively enhanced incorporation efficiency for liposomes of cancer cells. On the contrary, TEMPO incorporation efficiency in the same liposomes of cancer cells was not much different compared to healthy cells. Data indicate that TEMPO-benzoate as a probe is more suitable than TEMPO to discriminate cancer cells from healthy cells. Free energy gain observed for TEMPO-benzoate resulted mainly from the hydrophobic effect of the benzoate group.

Inhibitory Effects of Selected Medicinal Plants on Bacterial Growth of Methicillin-Resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is a serious threat to global public health due to its capacity of tolerate conventional antibiotics. Medicinal plants are traditionally used to treat infectious diseases caused by bacterial pathogens. In the present study, 16 medicinal plants were screened for antibacterial activities to preselect more effective species. Ethanol extracts of selected medicinal plants (Caesalpinia sappan L., Glycyrrhiza uralensis Fisch., Sanguisorba officinalis L., and Uncaria gambir Roxb) were partitioned successively with different solvents (n-hexane, chloroform, ethyl acetate, 1-butanol, and water). Disc diffusion assay and broth microdilution were performed to evaluate the antibacterial activities of plant extracts and fractions against Staphylococcus aureus strains. Furthermore, the cytotoxicity of the extracts and fractions was determined against the human hepatoma (HepG2) and human lung carcinoma (A549) cell lines using a trypan blue exclusion method. A few extracts and fractions showed significant inhibitory effects on the bacterial growth of all tested strains, including multidrug-resistance (MDR) clinical isolates. The ethyl acetate fraction of C. sappan had the most potent effects with minimum inhibitory/bactericidal concentrations (MIC/MBC) of 31.2/62.5 μg/mL and showed low cytotoxicity with over 90% cell viability in both cells. Our results suggest that medicinal plants have considerable potential as alternatives to conventional antibiotics.

Efficient Synthesis of Densely Functionalized Pyrido[2,3-d]Pyrimidines via Three-component One-pot Domino Knoevenagel aza-Diels Alder Reaction and Induces Apoptosis in Human Cancer Cell Lines via Inhibiting Aurora A and B Kinases

The identification of novel aurora kinase inhibitors is one of the most attractive directions in the field of anticancer research and development. In our ongoing efforts to pursue the class of inhibitors, a series of pyrido[2,3-d]pyrimidines were synthesized in DIPEAc/EtOH media. The advantages of the present methodology include a one-pot multicomponent environmentally friendly approach, cost effectiveness, broad substrate scope, operational simplicity, short reaction times, easy workup procedure and high yields. Synthesized compounds were screened against human lung carcinoma A549 cells, human hepatocellular liver carcinoma HepG2 cells and human cervical carcinoma epithelial HeLa cells. Compound 6 b i.e. diethyl 5-(4-methoxyphenyl)-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6,7-dicarboxylate was found to be equipotent than the standard drug VX-680 against selected cancer cell lines. The selected compounds (6b, 6d and 6h) exhibit potent inhibition against Aurora A and B with IC50 values (9.4–25 mg/L). Molecular docking model showed that the compounds can bind well to the target by interacting with amino acid residues. It will provide some valuable information for the commercial Aurora Kinase inhibitors.

Chemical proteomics reveals interactors of the alarmone diadenosine triphosphate in the cancer cell line H1299.

Intracellular dinucleoside polyphosphates (Npn Ns) have been known for decades but the functional role remains enigmatic. Diadenosine triphosphate (Ap3 A) is one of the most prominent examples, and its intercellular concentration was shown to increase upon cellular stress. By employment of previously reported Ap3 A-based photoaffinity-labeling probes (PALPs) in chemical proteomics, we investigated the Ap3 A interactome in the human lung carcinoma cell line H1299. The cell line is deficient of the fragile histidine triade (Fhit) protein, a hydrolase of Ap3 A and tumor suppressor. Overall, the number of identified potential interaction partners was significantly lower than in the previously investigated HEK293T cell line. Gene ontology term analysis revealed that the identified proteins participate in similar pathways as for HEK293T, but the percentage of proteins involved in RNA-related processes is higher for H1299. The obtained results highlight similarities and differences of the Ap3 A interaction network in different cell lines and give further indications regarding the importance of the presence of Fhit.