Human Lung Carcinoma Cell Line Research Articles

Investigation on the pharmacological profile for new synthesized bis heterocyclic analogs containing nitrogen atom as anti-cancer therapy target

Cancer is a common public health disease causing mortality worldwide. Thus, providing novel chemotherapies that tackle breast cancer is of great interest. In this investigation, novel heterocyclic compounds with pyridine, pyrimidine, and pyrazole rings 2–16 were synthesized and characterized using a variety of spectrum analyses. All synthesized compounds were evaluated for their anticancer effects on human lung carcinoma cell line (H460), human pharynx squamous cell carcinoma cell line (FaDu), and common human hepatocellular carcinoma cell line (Huh7), compounds 3 (6-ethoxy-pyridine), 8 (pyridinyl-pyrazol), 9 (pyridinyl-N, N-diacetylpyrazol), 11 (pyridinyl-N-(2,4-dinitrophenyl)pyrazole), 13 (pyridinyl-isoxazole) and 16 (pyridinyl-benzo[b][1,4]thiazepine) had the maximum anticancer activity against all examined cell lines. Based on these resultss, we are able to conclude that analoges 6-Ethoxy-pyridine 3, Pyridinyl-pyrazol 8, Pyridinyl-N-(2,4-dinitrophenyl)pyrazole 11 and Pyridinyl-benzo[b][1,4]thiazepine 16 are found to be secure and specific because their IC50 values on normal cell line are higher than their IC50 values on tested cancer cell lines.

Silencing RNA-Mediated Knockdown of IFITM3 Enhances Senecavirus A Replication.

Senecavirus A (SVA) is a non-enveloped, positive sense, single-stranded RNA virus that causes vesicular diseases in pigs. Interferon-induced transmembrane 3 (IFITM3) is an interferon-stimulated gene (ISG) that exhibits broad antiviral activity. We investigated the role of IFITM3 in SVA replication. Both viral protein expression and supernatant virus titer were significantly increased when endogenous IFITM3 was knocked down by approximately 80% in human non-smallcell lung carcinoma cell line (NCI-H1299) compared to silencing RNA control. Interestingly, overexpression of exogenous IFITM3 in NCI-H1299 cells also significantly enhanced viral protein expression and virus titer compared to vector control, which was positively correlated with induction of autophagy mediated by IFITM3 overexpression. Overall, our results indicate an antiviral role of endogenous IFITM3 against SVA. The exact molecular mechanisms by which endogenous IFITM3 limits SVA replication remain to be determined in future studies.

Abstract 4439: Decoding the metabolic symphony TP53 mutation-driven rewiring of cellular metabolism in non-small cell lung carcinoma

Abstract TP53 is a critical regulator of major metabolic pathways. Metabolic reprogramming is one of the "hallmarks of cancer" and drives tumorigenesis. Frequent p53mutations not only eradicate tumour suppressor capacities but also confer various activities that impact the alteration of metabolic pathways now regarded as central for tumour development and progression. We selected three hotspot mutants (R175H, R273H and R249S) and wtp53 to evaluate the effects in the human non-small cell lung carcinoma cell line (NCI-H1299). Differential expressions of p53 mutants were observed in normal and glucose/glutamine starvation. However, WTp53 expression was not found to be affected. Under both the glucose and glutamine starvation, inhibition of the cell growth and migratory potential of mutant cells was observed which was more prominent in glutamine starvation. Basal respiration and ATP production in p53-/- R273H and R249S significantly increased under glucose starvation. However, Non-mitochondrial oxygen consumption and maximal respiration were found to be decreased in all the cell lines. Importantly, the cells harbouring mutation R175H increase the glycolysis and TCA cycle. The metabolic intermediates of the urea cycle were found to be increased by nearly fourfold in R273H cells. Indicating increased utilization of the urea cycle instead of the TCA cycle, which has been known to be fueled by glutamine for anaplerosis. This study demonstrates that mutp53 influences several metabolic processes and has an influence on cancer cell aggression under starvation of main carbon sources (Glucose and Glutamine). In starved conditions, cells with p53 mutations enhance mitochondrial activity and use alternative pathways in non-small cell lung cancer cells. This might provide a foundation for the development of more effective targeted therapeutics/pharmacological approaches toward variants of mutant p53. Citation Format: Jiyauddin Khan, Asad Ur Rehman, Ankit Mathur, Naveen Kumar Bhatrajuc, Anannya Tulid, Divya Rajput, Mohammad Askandar Iqbal, Daman Saluja. Decoding the metabolic symphony TP53 mutation-driven rewiring of cellular metabolism in non-small cell lung carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4439.

In vitro EVALUATION of THE EFFECTS of POTENTIAL GSK-3β INHIBITORS TERBUTALINE and ORCIPRENALINE

Lung cancer is a type of cancer that is mostly diagnosed at an advanced stage and has a short survival time despite standard chemotherapy and targeted therapies. Terbutaline and Orciprenaline are bronchodilator agent that are potent and selective β2 receptor agonists. The purpose of this study was to investigate by continuous monitoring to assay the effects of Terbutaline and Orciprenaline on human lung carcinoma cell line. Cells were treated 1, 10, 100, 200, 400 µM concentrations with Terbutaline/Orciprenaline. MTT assay and xCELLigence real-time cell analyzer were used to determine these compounds effect on cell viability. The cell index was monitored continuously by visualizing the impedance of the E-plate wells. Because of GSK3β roles in a diverse range of cellular processes like metabolism, cell proliferation, differentiation and survival and its key position at several signaling pathways, GSK3β inhibition was investigated of these molecules. It has been determined that Terbutaline and Orciprenaline inhibits GSK-3β.
 This is the first known study to demonstrate the effects of Terbutaline and Orciprenaline on A549 and the human bronchial epithelial cell line Beas-2b in real time. In this study, it was detected that Terbutaline and especially Orciprenaline may have potential therapeutic effects in lung carcinoma.

Vincazalidine A, a unique bisindole alkaloid from Catharanthus roseus.

A new dimeric indole alkaloid, vincazalidine A consisting of an aspidosperma type and a modified iboga type with 1-azatricyclo ring system consisting of one azepane and two piperidine rings coupled with an oxazolidine ring was isolated from Catharanthus roseus, and the structure including absolute stereochemistry was elucidated on the basis of spectroscopic data as well as DP4 statistical analysis. Vincazalidine A induced G2 arrest and subsequent apoptosis in human lung carcinoma cell line, A549 cells.

New pyranopyrazole based derivatives: Design, synthesis, and biological evaluation as potential topoisomerase II inhibitors, apoptotic inducers, and antiproliferative agents

A new series of pyranopyrazole-based derivatives were designed and synthesized. The synthesized compounds were assessed for their cytotoxic efficacy against A549 human lung carcinoma and MCF-7 human breast carcinoma cell lines. Three compounds (1b, 4b, and 7b) exhibited 1.3- to 2.3-fold more antiproliferative activity than that of doxorubicin against the A549 cell line. In comparison to doxorubicin, compounds 1d and 3b were 4.1- and 1.04-fold, respectively more powerful against MCF-7 cancer cells. All the synthesized compounds were found to be more selective toward A549 cancer cells than the normal human fibroblast BJ cells. Of interest, compounds 1b and 7b exhibited promising cytotoxicity and SIs of 27.72 and 25.30, respectively, towards A549 cancer cells, higher than that of doxorubicin (SI 4.81). The most potent compounds 1b, 1d, 3b, 4b, and 7b were then subjected to in vitro Topo II inhibition assay. They showed IC50 values in the range of 2.07 to 8.86 µM. Of particular interest, compound 7b (IC50 = 2.07 µM), exhibited higher Topo II inhibitory activity than that of doxorubicin (IC50 = 2.56 µM). The significant Topo II inhibition of compound 7b was explained by molecular docking simulations into the Topo II active site. Compound 7b halted the cell cycle in the S phase in A549 cancer cells. It induced total apoptosis and necrosis of 20.73- and 4-fold, respectively, greater than the control. This evidence was supported by a 3.59-fold increase in the level of apoptotic caspase-9 and a remarkable elevation of the Bax/BCL-2 ratio. The physiochemical parameters of compound 7b were aligned with Lipinski’s rule of five.

Green synthesis of silver nanoparticles using Justicia adhatoda leaves extract and its anticancer effect on human lung carcinoma via induced apoptosis mechanism

In this study, Justicia adhatoda leaves extract was used to synthesize silver nanoparticles (AgNPs) and assess its anticancer attributes against human lung carcinoma (A549) cell line via induction of apoptosis mechanism. Initially, the biosynthesis of AgNPs was evident by observing the appearance of dark brown colour solution. UV–Vis spectrum showed characteristic surface plasmon resonance peak at 420 nm. FT-IR spectroscopy demonstrated the presence of distinct functional groups in both the extract and AgNPs. The peaks in XRD pattern corresponded to 101, 111, 200, and 220 crystal planes, thereby representing face-centred cubic silver. The EDX analysis confirmed the reduction of silver ions. The HR-SEM revealed spherical-shaped nanoparticles with an average size of 8–13 nm. In vitro cytotoxicity of extract and AgNPs was determined against A549 cell lines using MTT assay. The AgNPs revealed higher cytotoxity (59.25 ± 1.3–5.55 ± 1.3 %) than the extract (81.48 ± 1.3–16.66 ± 1.6 %) with reduced viabilities of cells at different concentrations. The IC50 values of the extract and AgNPs were calculated as 95.36 and 15.1 µg/mL, respectively. Apoptosis of AgNPs was analyzed using varied techniques as per the standard protocols. Acridine orange staining showed reduced green fluorescence of A549 cells due to the action of AgNPs. DNA fragmentation assay revealed the breakage of DNA double strands of cells and yielded laddered pattern. Flow cytometry analysis depicted increment in the cells count in S phase and concomitant decrement in Go/G1 phase. Quantitative real-time PCR demonstrated the upregulation and downregulation of Bax and Bcl-2 genes, respectively. Additionally, the exposure of A549 cells with AgNPs induced cytochrome C production from depolarized mitochondrial membrane into cytosol, which further upregulated caspase-9 and caspase-3 genes. In conclusion, J. adhatoda leaves-mediated AgNPs induced the apoptosis mechanism in A549 lung adenocarcinoma cells and indicated its paramount role as an effectual anticancer agent in future nanomedicine.

Long-term shelf-life liposomes for delivery of prednisolone and budesonide

Liposomes are nanoscale drug delivery systems built up from lipid layers and are able to spontaneously self-assemble in an aqueous environment. Both hydrophilic and hydrophobic drugs can be delivered by liposomes and this kind of nanoformulation offers many advantages regarding biodistribution, drug absorption and controlled drug release. Corticosteroids as lipophilic molecules are able to integrate into the lipid bilayer. This novel approach can improve the efficacy of several anti-inflammatory, such as asthma therapy.Our aim was to create liposomes with long shelf-life, which can incorporate and release corticosteroids such as Prednisolone (Pred) and Budesonide (Bud) at the temperature of inflamed tissues. Two kinds of liposome samples were prepared from three different kinds of phospholipids to get unilamellar vesicles with 100 nm in diameter and characterize their physicochemical properties and effect on living cells. Their main phase transition temperature in the physiologically relevant temperature range was measured by differential scanning calorimetry. According to the size distributions determined by dynamic light scattering, all drug-containing liposomes were stable for 6 months. All of the liposome types have a slightly negative zeta potential value. The Fourier-transform infrared spectroscopy revealed no chemical interaction between the drug and lipid molecules. The entrapment efficacy was determined by size-exclusion gel chromatography combined with UV–VIS spectrophotometry and it was very high in both cases (between 70 and 87%). The drug leakage was 35–40% for Pred and 6–8% for Bud in the first 30 min. The effect of liposomal drugs on cell viability was measured on the EBC-1 human lung carcinoma cell line. Neither the free corticosteroids nor their liposomal form were toxic to the cells. The cellular internalization of the liposomes was proved by flow cytometry and confocal microscopy.In summary, these liposomes could be useful in the delivery of corticosteroids (Pred or particularly Bud) in more effective asthma therapy, having fewer side effects due to the nanoformulation.

Design, synthesis and bioevaluation of novel prenylated chalcones derivatives as potential antitumor agents

A series of novel prenylated chalcone derivatives with broad spectrum anticancer potential were designed and synthesized. Some of the synthesized target compounds showed potent anti-proliferative activities toward LNCaP (prostate cancer cell line), K562 (human leukemia cells), A549 (human lung carcinoma cell line) and HeLa (cervical cancer cell line) cell lines. Among of the active compounds, (E)-1-(4-(2-(diethylamino)ethoxy)-2-hydroxy-6-methoxy-3-(3-methylbut-2-en-1-yl)phenyl)-3-(pyridin-3-yl)prop-2-en-1-one (C36) was directly interacted with protein kinase B (PKB), also known as AKT, significantly inhibited the pPI3K, pAKT(Ser473) protein levels to repress the growth of cancer cells by inducing apoptosis, arresting cell cycle. Our studies provide support for prenylated chalcone derivatives potential applications in cancer treatment as a potential AKT inhibitor.

LCMR1 Promotes Large-Cell Lung Cancer Proliferation and Metastasis by Downregulating HLA-Encoding Genes.

Lung cancer is notorious for its high global morbidity and mortality. Here, we examined whether the LCMR1 gene, which we previously cloned from a human large-cell lung carcinoma cell line, contributes to the proliferation and metastasis of large-cell lung carcinoma. To this end, we performed pan-cancer and non-small cell lung cancer (NSCLC) cell line-based LCMR1 expression profiling. Results revealed that LCMR1 was expressed at high levels in most solid tumors, including NSCLC. LCMR1 expression was the highest in the 95D large cell lung cancer cell line. Functional studies using lentivirus-based knockdown revealed that LCMR1 was critical for the proliferation, migration, and invasion of cultured large cell lung cancer cells. Moreover, blocking this gene significantly reduced tumor growth in a 95D cell xenograft mouse model. A multiple sequence-based assay revealed a mechanism by which LCMR1 diminished the RNA Pol II occupancy at the promoter of human leukocyte antigen (HLA)-encoding genes to prevent their transcription. The HLA genes play vital roles in cancer-specific antigen presentation and anticancer immunity. A correlation assay using TCGA database identified a negative relationship between the expression levels of LCMR1 and HLA coding genes. Taken together, our findings demonstrate that LCMR1 is required for large cell lung cancer cell growth and invasion and suggest its potential as a valid target in clinical treatment.

Conditioned media of tonsil derived mesenchymal stem cells shows different rates of cytotoxicity on solid cancer cells

Aims: Mesenchymal stem cells (MSCs) are the apple of the eye of cancer studies. It was indicated that the secreted factors, especially released by MSCs, have tumoral or anti-tumoral effects on tumor progression. MSCs obtained from different sources show different anti-tumoral effects, while MSCs originating from the same source also show different tumoral effects in different cancer cells. Here, we investigated the anti-tumor effects of soluble factors secreted from palatine tonsil MSCs (TMSC) as a new source of MSC on human lung carcinoma (A549) and pancreatic cancer (PANC-1) cell lines.
 Methods: Conditioned medium (CM) was obtained from TMSCs isolated from palatine tonsil tissue, and the cytotoxic effect of CM on the growth of A549 and PANC-1 in a dose-dependent manner was demonstrated by MTT analysis. In addition, the function of CM treatment on the cell cycle status of cancer cells and the apoptosis process were investigated through cell cycle analysis with propidium iodide (PI) and Annexin-V/PI detection method by flow cytometry analysis, respectively. 
 Results: We demonstrated that TMSC-CM treatment significantly decreased the viability of A549 and PANC-1 cell lines in a dose-dependent manner post-48 hours. In addition, CM treatment differentially induced the apoptosis on A549 and PANC-1 cells and also, caused G2/M arrest in the cells.
 Conclusion: In light of these findings, our study is the first to show that TMSC-CM has an anti-tumoral effect by stimulating apoptosis on A549 and PANC-1 cells. These findings reveal that the usage of CM has a cell-free cellular therapeutic potential.

Formulation optimization of pH-sensitive liposomes based drug delivery of Carboplatin and anti-proliferative evaluation against A549 (human lung carcinoma) cell lines

The developments of pH–sensitive liposomes which are stable at physiological pH i.e. (6.8–7.4) have not explored much up until now. These lipid vesicles will go through destabilization and attain fusogenic properties in acidic conditions leading to liberation of aqueous contents. Carboplatin, included in the family of alkylating agent was found to exhibit adverse effects like myelo suppression, ion thrombocytopenia and leucopenia. Therefore, in order to circumvent these effects, carboplatin pH-sensitive liposomes for specific delivery is the ideal criteria and it poses a great challenge since the water-soluble drugs exhibited very low entrapment efficiency. The essential portion of study was evaluated using the Design Expert software 8. The pH-sensitive liposomes were optimized using Central composite design and one factor Response surface model design method and were prepared by film hydration method. Two formulation variables like drug: lipid ratio (X1) and volume of hydration media (X2) used to vary at three different levels and the other three variables viz. temperature, speed of rotation and vacuum applied were kept constant. The Response surface and contour plots were figured to elicit the effects of interaction of variables on the overall entrapment efficiency. pH-sensitive liposomes of carboplatin have been regarded as a promising delivery systematic approach in order to target tumor tissue as evaluated by the pre-clinical studies in both in vitro and ex-vivo conditions.

Seven new secondary metabolites isolated from roots of Lespedeza bicolor

Chemical investigation of a methanol extract obtained from the roots of Lespedeza bicolor identified one new pterocarpene (1), three new pterocarpans (2–4), and three new arylbenzofurans (5–7), and two known compounds (8 and 9). Their structures were determined by interpretations obtained from combined UV, NMR, and HRTOFMS spectroscopic data. Furthermore, the absolute configurations of compounds 2 and 3 were established by the combination of electronic circular dichroism (ECD) calculations and NMR calculations with DP4+ probability analysis. All isolated compounds (1–9) were evaluated for cytotoxicity against the human lung carcinoma cell line A549 and the human hepatoma cell line Huh-7. Compound 4 showed antiproliferative activity against A549 cell line with IC50 value of 24.9 μM. Furthermore, compound 9 exhibited cytotoxicity against Huh-7 cell line with IC50 value of 68.7 μM.

Experimental and molecular docking investigation of anticancer activity of new mixed-ligand Schiff base complexes against human colorectal (HCT116), lung (A549) and breast (MCF7) carcinoma cell lines

New mixed-ligand Cu(II) complexes, [Cu(SB)L1–3]ClO4, that contain a tridentate NN'O type unsymmetrical Schiff-base main ligand (SB) and a heterocyclic co-ligand (L) (py in (1), bpy in (2) and phen in (3)) were synthesized and characterized. The SB is the product of 1:1 condensation between 1,3-propanediamine with 2‑hydroxy-4-methoxybenzaldehyde, which was formed during the template synthesis of complex (1). Complexes (2) and (3) were obtained by the exchange of monodentate py with bidentate bpy or phen, respectively. The crystal structure of (2) was obtained by single-crystal x-ray crystallography (SCXRC). From the crystal structure, (2) is pentacoordinated with square-based pyramidal geometry around Cu(II). The anticancer activity of the complexes was studied against three human carcinoma cell lines. All the complexes showed a potent cytotoxic effect on the Human colorectal (HCT116), lung (A549) and breast (MCF7) cancerous cells that exert their cytotoxicity in a dose and time dependent manner. Among these complexes, (2) had the highest cytotoxicity that made it a promising candidate for developing new anticancer drugs. The IC50 values for (2) were 4.16, 4.97 and 7.82 μM against A549, MCF7 and HCT116, respectively, after 48 h of incubation. The IC50 values order were (2)<(1)<(3) in each cell line. Molecular docking studies were also performed on A549 (PDB ID: 4zxt), HCT116 (PDB ID: 3ruk) and MCF-7 (PDB ID: 4zvm) human carcinoma cells' proteins. Based on the estimated free binding energy (EFBE) good correlation was observed with the obtained experimental data.

Alternaria alternata F3, a Novel Taxol-Producing Endophytic Fungus Isolated from the Fruits of Taxus cuspidata: Isolation, Characterization, Taxol Yield Improvement, and Antitumor Activity.

In this study, a novel taxol-producing endophytic fungus, strain F3, was isolated from the fruits of Taxus cuspidata and identified as Alternaria alternata according to its macroscopic and microscopic traits and sequence analysis of internal transcribed spacer (ITS). The presence of taxol was detected by thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC) and confirmed by ultra-high-performance liquid chromatography-electrospray coupled to tandem mass spectrometry (UPLC-ESI-MS/MS) and nuclear magnetic resonance (NMR). The fermentation parameters of strain F3 were then optimized for high taxol production. The maximum taxol yield of 195.4µg L-1 by A. alternata F3 was observed in 200-mL yeast peptone dextrose (YPD) broth, at an initial pH value of 6.0, supplemented with 0.1g L-1 sodium acetate, 0.25g L-1 salicylic acid, and 0.00125g L-1 silver nitrate and inoculum size 2%, and incubated at 28°C and 150rpm for 8days, which was 2.12-fold compared with the initial yield of taxol. Also, fungal taxol exhibited antitumor activity towards human lung carcinoma (A549) cell line and human cervical carcinoma (Hela) cell line with IC50 values of 3.98µgmL-1 and 0.35µgmL-1. Overall, this is the first report on taxol-producing endophytic fungus isolated from the fruits of Taxus. This study offers a novel source for the production of taxol for anticancer treatment.

In Silico and In Vitro Assessment of Carbonyl Reductase 1 Inhibition Using ASP9521-A Potent Aldo-Keto Reductase 1C3 Inhibitor with the Potential to Support Anticancer Therapy Using Anthracycline Antibiotics.

Anthracycline antibiotics (ANT) are among the most widely used anticancer drugs. Unfortunately, their use is limited due to the development of drug resistance and cardiotoxicity. ANT metabolism, performed mainly by two enzymes-aldo-keto reductase 1C3 (AKR1C3) and carbonyl reductase 1 (CBR1)-is one of the proposed mechanisms generated by the described effects. In this study, we evaluated the CBR1 inhibitory properties of ASP9521, a compound already known as potent AKR1C3 inhibitor. First, we assessed the possibility of ASP9521 binding to the CBR1 catalytic site using molecular docking and molecular dynamics. The research revealed a potential binding mode of ASP9521. Moderate inhibitory activity against CBR1 was observed in studies with recombinant enzymes. Finally, we examined whether ASP9521 can improve the cytotoxic activity of daunorubicin against human lung carcinoma cell line A549 and assessed the cardioprotective properties of ASP9521 in a rat cardiomyocytes model (H9c2) against doxorubicin- and daunorubicin-induced toxicity. The addition of ASP9521 ameliorated the cytotoxic activity of daunorubicin and protected rat cardiomyocytes from the cytotoxic effect of both applied drugs. Considering the favorable bioavailability and safety profile of ASP9521, the obtained results encourage further research. Inhibition of both AKR1C3 and CBR1 may be a promising method of overcoming ANT resistance and cardiotoxicity.

Synthesis, crystal structure, computational investigation, molecular docking analysis and anti-lung cancer activity of novel (Z)-3-amino-2-(cyclohexylidenehydrazono)thiazolidin-4-one

Ever since the disease of cancer was discovered, man has been mystified by both its mysterious origin and the even more mystifying mechanisms by which it spreads. Although advances in surgery and radiotherapy have significantly impacted cancer treatment, the idea of systemic chemotherapy which is targeted specifically at cancer cells and has minimal side effects remains a strategic goal for the future. A novel thiazolidin-4-one analogue was synthesized by the reaction of 1,2,4,5-tetraazaspiro[5.5]undecane-3-thione with chloroacetic acid. The newly synthesized compound was investigated theoretically as well as experimentally by FT-IR, 1H, 13C NMR and UV–Vis spectra and biologically screened in vitro for its anti-lung cancer activity against A549 cancer cell line. The crystal structure of (Z)-3-amino-2-(cyclohexylidenehydrazono)thiazolidin-4-one has been determined by single crystal X-ray diffraction and revealed that it belongs to monoclinic system with cell dimensions: a = 18.9393 (16) Å, b = 5.2747 (4) Å, c = 10.9518 (9) Å, α = 90°, β = 90.214 (3), γ = 90° and V = 1082.85 (15) Å3. Hirshfeld surface analysis was performed to study the nature of intermolecular interactions within the crystal structure via 3D and 2D fingerprint surfaces and to demonstrate H-bonding with close contacts in crystal via dnorm surface. A descriptive study of (Z)-3-amino-2-(cyclohexylidenehydrazono)thiazolidin-4-one was done by using density functional theory at DFT/B3LYP/6–311 ++G (d,p) basis set. Results of NLO analysis, ELF, LOL, NCI, AIM, HOMO-LUMO, first hyperpolarizability and molecular electrostatic potential were reported. Theoretical calculation of ADMET properties suggested that the synthesized compounds have a good pharmacokinetic profile. The results of cytotoxic evaluation indicated that (Z)-3-amino-2-(cyclohexylidenehydrazono)thiazolidin-4-one has broad-spectrum cytotoxic activity with IC50 values of 240 μM against Human lung carcinoma cell line (A549).

Surface PEGylation of ZIF-8 metal-organic framework based on magnetic hydroxyapatite as a pH/magnetic targeting responsive system for anticancer drug delivery

In the present study, a zinc-based metal-organic framework/magnetic hydroxyapatite nanocomposite (Fe3O4@SiO2@HAp@ZIF-8) as new targeting drug delivery system was synthesized through the solvothermal method. Then, Fe3O4@SiO2@HAp@ZIF-8 was coated with a biocompatible layer of polyethylene glycol (PEG) (Fe3O4@SiO2@HAp@ZIF-8-PEG). The structural features of these nanocomposites were characterized using FT-IR, XRD, FE-SEM, EDX, TEM, Zeta potential, BET, and VSM analysis. The Fe3O4@SiO2@HAp@ZIF-8 and Fe3O4@SiO2@HAp@ZIF-8-PEG were applied as a carrier to encapsulate the doxorubicin (DOX) as an anticancer drug. The drug loading capacity and encapsulation efficiency of Fe3O4@SiO2@HAp@ZIF-8 and Fe3O4@SiO2@HAp@ZIF-8-PEG were 7.6, 76.09, 9.8, and 98.12%, respectively. Moreover, a drug release study revealed that both nanocomposites were pH-dependent because of the dissolution of HAp under acidic conditions. The release kinetics of DOX from the prepared nanocomposites at pH 5 also showed that the Korsmeyer-Peppas model was the best model to describe the release mechanism of DOX from prepared systems. The in vitro cell viability results showed that synthesized systems had no significant toxicity, while DOX-loaded systems had notable and higher toxicity against A549 human lung carcinoma cell lines. The DPPH tests also showed that the prepared Fe3O4@SiO2@HAp@ZIF-8-PEG nanocomposites have excellent antioxidant activity. Therefore, all obtained results clearly suggest that the as-prepared drug systems are potential and suitable candidates for targeted drug delivery applications.

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.