Normal Lung Fibroblast Cell Line Research Articles

Design, synthesis, molecular modelling and biological evaluation of novel 6-amino-5-cyano-2-thiopyrimidine derivatives as potent anticancer agents against leukemia and apoptotic inducers

Herein, a novel series of 6-amino-5-cyano-2-thiopyrimidines and condensed pyrimidines analogues were prepared. All the synthesized compounds (1a-c, 2a-c, 3a-c, 4a-r and 5a-c) were evaluated for in vitro anticancer activity by the National Cancer Institute (NCI; MD, USA) against 60 cell lines. Compound 1c showed promising anticancer activity and was selected for the five-dose testing. Results demonstrated that compound 1c possessed broad spectrum anti-cancer activity against the nine cancerous subpanels tested with selectivity ratio ranging from 0.7 to 39 at the GI50 level with high selectivity towards leukaemia. Mechanistic studies showed that Compound 1c showed comparable activity to Duvelisib against PI3Kδ (IC50 = 0.0034 and 0.0025 μM, respectively) and arrested cell cycle at the S phase and displayed significant increase in the early and late apoptosis in HL60 and leukaemia SR cells. The necrosis percentage showed a significant increase from 1.13% to 3.41% in compound 1c treated HL60 cells as well as from 1.51% to 4.72% in compound 1c treated leukaemia SR cells. Also, compound 1c triggered apoptosis by activating caspase 3, Bax, P53 and suppressing Bcl2. Moreover, 1c revealed a good safety profile against human normal lung fibroblast cell line (WI-38 cells). Molecular analysis of Duvelisib and compound 1c in PI3K was performed. Finally, these results suggest that 2-thiopyrimidine derivative 1c might serve as a model for designing novel anticancer drugs in the future.

Transcription Silencing and CpGs Hypermethylation as Therapeutic Gene Editing in Clinical Colorectal Adenocarcinoma Repression.

Colorectal cancer is the most common cancer in oncopathology, with an increasing incidence among the elderly during the last decade. Various genetic and environmental factors play important roles in the emergence of colorectal adenocarcinoma. Non-coding RNAs, approximately 20-22 nucleotides, are transcribed irregularly in many cancer cells and play a critical role in many metabolic pathways in clinical cancer cases. DNA methylation is a critical epigenetic alteration that controls gene expression. In the current study, transcriptional silencing and CpG hypermethylation were developed as a therapeutic gene editing strategy for the clinical repression of colorectal adenocarcinoma. A human colorectal adenocarcinoma cell line (Caco2) and a normal lung fibroblast cell line (Wi38) were utilized as the paradigms in this research to examine the effect of mir155 molecule transfection and CpGs-island (CGI) methylation. Cell counting was achieved using six-well and 24-well plates before transfection using a hemocytometer. The two cell lines were transfected with the mir155 agomir and antagomir molecules. The transfection efficiency, cell viability, cell IC50, and target gene expression were measured, and CGIs-methylation was achieved by bisulfate conversion. The outcomes revealed the downregulation of oncogenes (AKT1 and VCAM1 genes as cancer-associated genes) and the upregulation of tumor suppressor genes (TSGs, Tp53 and KEAP1). In addition, CpG-islands methylation showed significant blocking of the oncogene promoter regions, and the switch on of TSG promoter regions was continuous. miRNA-CGI-methylation led to the regression of Caco2 cell proliferation, suggesting the potential use of RNA silencing and DNA methylation in targeted gene therapy for colorectal cancer.

Nanostructure Lipid Carrier of Curcumin Co-Delivered with Linalool and Geraniol Monoterpenes as Acetylcholinesterase Inhibitor of Culex pipiens.

(1) Background: A molecular hybridization docking approach was employed to develop and detect a new category of naturally activated compounds against Culex pipiens as acetylcholinesterase inhibitors via designing a one-pot multicomponent nano-delivery system. (2) Methods: A nanostructure lipid carrier (NLC), as a second generation of solid lipid nanoparticles, was used as a carrier to deliver the active components of curcumin (Cur), geraniol (G), and linalool (L) in one nanoformulation after studying their applicability in replacing the co-crystallized ligand imidacloprid. (3) Results: The prepared nanostructure showed spherical-shaped, polydisperse particles ranging in size from 50 nm to 300 nm, as found using a transmission electron microscope. Additionally, dynamic light scattering confirmed an average size of 169 nm and a highly stable dispersed solution, as indicated by the zeta potential (-38 mV). The prepared NLC-Cur-LG displayed competitive, high-malignancy insecticidal activity against fourth instar C. pipiens with an elevated rate of death of 0.649 µg/mL. The treatment, due to the prepared nanostructure, affects oxidative stress enzymes, e.g., hydrogen peroxide (4 ppm), superoxide dismutase (SOD) (0.03 OD/mg), and protein carbonyl (0.08 OD/mg), and there are observable upward and downward fluctuations when using different concentrations of NLC-Cur-LG, suggesting significant problems in its foreseeable insecticidal activity. The acetylcholinesterase activity was assessed by an enzyme inhibition assay, and strengthened inhibition occurred due to the encapsulated NLCs (IC50 = 1.95 µg/mL). An investigation of the gene expression by Western blotting, due to treatment with NLC-Cur-LG, revealed a severe reduction of nearly a quarter of what was seen in the untreated group. As a preliminary safety step, the nanoformulation's toxicity against normal cell lines was tested, and a reassuring result was obtained of IC50 = 158.1 µg/mL for the normal lung fibroblast cell line. (4) Conclusions: the synthesized nanoformulation, NLC-Cur-LG, is a useful insecticide in field conditions.

In Vitro and In Silico Studies on Benzimidazole‐Based Compounds

AbstractColon cancer remains a significant health concern, necessitating the synthesis of novel therapeutic agents. Benzimidazole derivatives have shown promising anticancer potential. In this study, two benzimidazole derivatives were synthesized, and their antiproliferative activities were investigated in vitro against the human colon colorectal cancer cell line and the human normal lung fibroblast cell line. The cell viability revealed that molecule 3 had high antiproliferative activity and inhibited the growth of DLD‐1 cells for 48 h. Furthermore, molecule 3 was found to have more selectivity against the human normal cell line. Computational calculations were performed to predict the molecular properties of molecules using the B3LYP/6‐311++(2d,2p) density functional theory level. The quantum theory of atoms in molecules (QTAIM) and energy decomposition analysis (EDA) were utilized to investigate the nature of the interatomic bonding existing among the studied molecules. The ultraviolet‐visible (UV–vis) results for molecules were calculated using time‐dependent density‐functional theory (TD‐DFT). The chemical reactivity and molecular stability were also investigated by DFT computational analysis. The molecular docking and dynamics simulations were conducted, and their results reveal their concordance with the experimental results. Molecule 3 has better anti‐cancer activity against colon cancer targets (PDB ID: 2HQ6) compared to molecule 2.

Design, physicochemical confirmation, single crystal structures as well as exploration of antibacterial and anticancer potential of organotin(IV) carboxylates

In this article, we are reporting a series of di-and tri-organotin(IV) carboxylate complexes (1–4) derived from the reaction of sodium-3-bromophenylacetate (NaL) with (CH3)2SnCl2, (C4H9)2SnCl2, (CH3)3SnCl and (C4H9)3SnCl in dried toluene while refluxing for 8 h. The desired organotin(IV) derivative were analyzed by elemental analyzer, FTIR, NMR and single crystal XRD. The antimicrobial data against the tested bacterial strains follow the order: 2 > 4 > 3 > 1 > HL. The anticancer potential of the synthesized compounds was evaluated against the lung cancer cell line (A549) and normal lung fibroblast cell line (MRC-5) and it was observed that 4 was the highly cytotoxic against A549 while HL and 1 showed no cytotoxicity against MRC-5, neither at lower or higher concentrations.

A New Cu/Fe Layer Double Hydroxide Nanocomposite Exerts Anticancer Effects against PC-3 Cells by Inducing Cell Cycle Arrest and Apoptosis.

Prostate cancer treatment poses significant challenges due to its varying aggressiveness, potential for metastasis, and the complexity of treatment options. Balancing the effectiveness of therapies, minimizing side effects, and personalizing treatment strategies are ongoing challenges in managing this disease. Significant advances in the use of nanotechnology for the treatment of prostate cancer with high specificity, sensitivity, and efficacy have recently been made. This study aimed to synthesize and characterize a novel Cu/Fe layer double hydroxide (LDH) nanocomposite for use as an anticancer agent to treat prostate cancer. Cu/Fe LDH nanocomposites with a molar ratio of 5:1 were developed using a simple co-precipitation approach. FT-IR, XRD, SEM, TEM, TGA, and zeta potential analyses confirmed the nanocomposite. Moreover, the MTT cell viability assay, scratch assay, and flow cytometry were utilized to examine the prospective anticancer potential of Cu/Fe LDH on a prostate cancer (PC-3) cell line. We found that Cu/Fe LDH reduced cell viability, inhibited cell migration, induced G1/S phase cell cycle arrest, and triggered apoptotic effect in prostate cancer cells. The findings also indicated that generating reactive oxygen species (ROS) formation could improve the biological activity of Cu/Fe LDH. Additionally, Cu/Fe LDH showed a good safety impact on the normal lung fibroblast cell line (WI-38). Collectively, these findings demonstrate that the Cu/Fe LDH nanocomposite exhibited significant anticancer activities against PC-3 cells and, hence, could be used as a promising strategy in prostate cancer treatment.

Comparative study of antimicrobial potential and DNA/BSA binding affinity of silver(I) and gold(III) coordination compounds with 1,6-naphthyridine

In the present study, synthesis of silver(I) and gold(III) coordination compounds with 1,6-naphthyridine (1,6-naph), {[Ag(1,6-naph)(H2O)](BF4)}n (1) and [AuCl3(1,6-naph)] (2), was reported. The methods used for the structural characterization of a new compound 1 included IR, NMR (1H and 13C) and UV–Vis spectroscopy, cyclic voltammetry and single-crystal X-ray diffraction analysis. The crystallographic results showed that compound 1 represents silver(I) coordination polymer, in which 1,6-naph ligand acts as a bidentate bridging ligand connecting two Ag(I) ions via its N1 and N6 nitrogen atoms, while the third coordination site of the metal ion is occupied by the water oxygen atom, resulted in a T-shape geometry. Compounds 1 and 2 were evaluated in vitro for antimicrobial activity against five bacterial and two Candida species, while their cytotoxicity was tested on the normal human lung fibroblast cell line (MRC-5). Compound 1 has manifested a remarkable antifungal activity on both tested Candida strains (C. albicans and C. parapsilosis) with minimal inhibitory concentrations (MICs) of 1.43 and 11.38 µM (0.49 and 3.9 µg/mL), respectively, while no significant antimicrobial activity was observed for 2. Moreover, silver(I) coordination polymer 1 inhibits the hyphae formation of C. albicans at subinhibitory concentration. The binding affinity of both compounds 1 and 2 with calf thymus DNA (ct-DNA) and bovine serum albumin (BSA) was studied by fluorescence spectroscopy, indicating their ability to interact with these biomolecules, with compound 2 being more reactive.

Targeting SOX18 Transcription Factor Activity by Small-Molecule Inhibitor Sm4 in Non-Small Lung Cancer Cell Lines

The transcription factor SOX18 has been shown to play a crucial role in lung cancer progression and metastasis. In this study, we investigated the effect of Sm4, a SOX18 inhibitor, on cell cycle regulation in non-small cell lung cancer (NSCLC) cell lines LXF-289 and SK-MES-1, as well as normal human lung fibroblast cell line IMR-90. Our results demonstrated that Sm4 treatment induced cytotoxic effects on all three cell lines, with a greater effect observed in NSCLC adenocarcinoma cells. Sm4 treatment led to S-phase cell accumulation and upregulation of p21, a key regulator of the S-to-G2/M phase transition. While no significant changes in SOX7 or SOX17 protein expression were observed, Sm4 treatment resulted in a significant upregulation of SOX17 gene expression. Furthermore, our findings suggest a complex interplay between SOX18 and p21 in the context of lung cancer, with a positive correlation observed between SOX18 expression and p21 nuclear presence in clinical tissue samples obtained from lung cancer patients. These results suggest that Sm4 has the potential to disrupt the cell cycle and target cancer cell growth by modulating SOX18 activity and p21 expression. Further investigation is necessary to fully understand the relationship between SOX18 and p21 in lung cancer and to explore the therapeutic potential of SOX18 inhibition in lung cancer.

Nanostructured γ-Al2O3 Synthesis Using an Arc Discharge Method and its Application as an Antibacterial Agent against XDR Bacteria

In the last few years, many efforts have been devoted to investigating the antibacterial activity of metal nanoparticles, especially against multidrug-resistant bacteria. Recently extensively drug-resistant (XDR) bacteria have emerged and caused a global threat. The purpose of this manuscript was to synthesize nanostructured γ-Al2O3 as an antibacterial agent against some XDRs. The results showed that Al2O3 was a mix of rod and spherical shapes in the nano range with diameters of less than 30 nm. The zeta potential was determined to estimate the surface charge for the synthesized γ-Al2O3, which was recorded as −34 ± 1.8 mV, indicating good stability. The synthesized nanostructured γ-Al2O3 showed a potent antibacterial activity against extensively drug-resistant Acinetobacter baumanii, with an inhibition zone diameter that reached 19 mm and a minimum inhibitory concentration (MIC) value that reached 2 µg/mL. The observed antibacterial activity of the prepared Al2O3 nanoparticles confirmed that the main mechanistic actions include bacterial cells apoptosis, ROS increment, cellular membrane disruption, and DNA damage. The cytotoxic effect (CC50) of the prepared γ-Al2O3-NPs was 1250 µg/mL in a normal human lung fibroblast cell line (WI-38 cells). It can be concluded that the synthesized γ-Al2O3 had an acceptable toxicity, which may pave the way for its use as a potent agent in the fight against XDR bacteria.

FAM3C in circulating tumor-derived extracellular vesicles promotes non-small cell lung cancer growth in secondary sites.

Rationale: Metastasis is a complex process with a molecular underpinning that remains unclear. We hypothesize that cargo proteins conducted by extracellular vesicles (EVs) released from tumors may confer growth and metastasis potential on recipient cells. Here, we report that a cytokine-like secreted protein, FAM3C, contributes to late-stage lung tumor progression. Methods: EV protein profiling was conducted with an unbiased proteomic mass spectrometry analysis on non-small cell lung cancer (NSCLC) and normal lung fibroblast cell lines. Expression of FAM3C was confirmed in a panel of NSCLC cell lines, and correlated to the invasive and metastatic potentials. Functional phenotype of endogenous FAM3C and tumor-derived EVs (TDEs) were further investigated using various biological approaches in RNA and protein levels. Metastasis potential of TDEs secreted by FAM3C-overexpressing carcinoma cells was validated in mouse models. Results: Transcriptomic meta-analysis of pan-cancer datasets confirmed the overexpression of FAM3C - a gene encoding for interleukin-like EMT inducer (ILEI) - in NSCLC tumors, with strong association with poor patient prognosis and cancer metastasis. Aberrant expression of FAM3C in lung carcinoma cells enhances cellular transformation and promotes distant lung tumor colonization. In addition, higher FAM3C concentrations were detected in EVs extracted from plasma samples of NSCLC patients compared to those of healthy subjects. More importantly, we defined a hitherto-unknown mode of microenvironmental crosstalk involving FAM3C in EVs, whereby the delivery and uptake of FAM3C via TDEs enhances oncogenic signaling - in recipient cells that phenocopies the cell-endogenous overexpression of FAM3C. The oncogenicity transduced by FAM3C is executed via a novel interaction with the Ras-related protein RalA, triggering the downstream activation of the Src/Stat3 signaling cascade. Conclusions: Our study describes a novel mechanism for FAM3C-driven carcinogenesis and shed light on EV FAM3C as a driver for metastatic lung tumors that could be exploited for cancer therapeutics.

Increased radical scavenging activity of thymoquinone and l-ascorbic acid dual encapsulated in palmitoyl-chitosan nanoparticles in a human normal lung fibroblast, MRC-5 due to synergistic antioxidative effects.

Less effective antioxidant supplementation in combating free radicals is often related to the lack of the formulation of carriers. The antioxidant may be one of the most powerful substances but is marred by poor uptake by cells when the carrier degraded and dissolved too rapidly. Nanoparticle (NP) systems are promising in overcoming the problem since they provide high surface area to enhance encapsulation and release efficiency. With the right selection of material, NP carriers could function as constructive antioxidant cargos. Generally, NPs carry only one active ingredient; this study, however, utilized chitosan nanoparticles (CNPs) and hydrophobically modified palmitoyl-chitosan nanoparticles (PCNPs) that were dual encapsulated with antioxidants of different polarities, namely, hydrophobic thymoquinone (TQ) and hydrophilic l-ascorbic acid (LAA) to evaluate their combination effects in scavenging free radicals. The antioxidants followed zero-order release kinetics with a controlled release manner for about 48 h. The interaction effects between TQ and LAA loaded in the NP systems were determined by classical isobologram (CI) values. The CI values were derived by a diphenyl picrylhydrazyl (DPPH) assay, a radical scavenging activity assay. Combined TQ and LAA had CI values of less than one, with a lower value in the PCNP system than in the CNP system. This indicates that the interaction between those antioxidants showed higher synergistic effects in PCNPs, which enhanced the DPPH radical scavenging activities. The antioxidative potential of compound(s) encapsulated in the PCNP carrier was further experimented by a reactive oxygen species (ROS) assay on a human normal lung fibroblast cell line (MRC-5) as lung is one of the organs with high accumulation of free radicals. About 48 h post treatment, the dual-loaded TQ and LAA in PCNPs showed the lowest ROS level in comparison to single-loaded antioxidants and bare antioxidant delivery. The hydrogen peroxide (H2O2) radical scavenging was influenced by both the controlled release property of the PCNP system and the synergy between TQ and LAA. In short, dual-loaded TQ and LAA in the hydrophobically modified PCNP had effectively depicted the capability of a single CS-based nanocarrier to hold more than one compound at a time to function as a potent radical scavenger.

Evaluation of In Vitro Cytotoxic Potential of Avarol towards Human Cancer Cell Lines and In Vivo Antitumor Activity in Solid Tumor Models.

The goal of this study was to determine the activity in vitro and in vivo of avarol, a sesquiterpene hydroquinone originating from the Dysidea avara sponge from the south Adriatic Sea, against different cancer cell lines and two types of mouse carcinoma. To investigate the in vitro cytotoxicity, a human cervix adenocarcinoma cell line (HeLa), human colon adenocarcinoma (LS174), human non-small-cell lung carcinoma (A549), and a normal human fetal lung fibroblast cell line (MRC-5) were used. The in vivo antitumor activity was investigated against two transplantable mouse tumors, the Ehrlich carcinoma (EC) and cervical cancer (CC-5). The effect of avarol on cancer cell survival, which was determined by the microculture tetrazolium test, confirmed a significant in vitro potency of avarol against the investigated cell lines, without selectivity towards MRC-5. The highest cytotoxicity was exhibited against HeLa cancer cells (10.22 ± 0.28 μg/mL). Moreover, potent antitumor activity against two tumor models was determined, as the intraperitoneal administration of avarol at a dose of 50 mg/kg resulted in a significant inhibition of tumor growth in mice. After three administrations of avarol, a 29% inhibition of the EC growth was achieved, while in the case of CC-5, a 36% inhibition of the tumor growth was achieved after the second administration of avarol. Therefore, the results indicate that this marine sesquiterpenoid hydroquinone could be a promising bioactive compound in the development of new anticancer medicine.

Arc discharge rapid synthesis of engineered copper oxides nano shapes with potent antibacterial activity against multi-drug resistant bacteria

Nowadays Nano metals have received an eminent compromise of attention. Even though different nanostructure of same metal maybe gives different results in wide range applications. Copper oxide (CuO-NPs) and Copper Nano wires (CuO-NWs) were prepared in controlled size via the alternating current Arc discharge process. Deionized water and argon gas were the chosen dielectric medium during the process to obtain 2 different forms of copper oxides. By changing the dielectric material from deionized water to argon gas the shape of CuO nanoparticles changed from spherical (CuO-NPs) to wires (CuO-NWS). The yield prepared depicted the purity of the prepared CuO, and their diameters were about 10 ± 5 nm and 30 ± 3 nm for CuO-NWs and CuO-NPs respectively. In vitro cytotoxic effect of the prepared CuO-NWs & CuO-NPs using human normal lung fibroblast cell line (WI-38 cells) revealed that CuO-NWs & CuO-NPs CC50 values were 458.8 and 155.6 µg/mL respectively. Both yields showed potent antibacterial activity against different multi-drug resistant Acinetobacter baumannii strains. A complete eradication of the bacterial growth was noticed after 4 Hrs incubation with CuO-NWs. Moreover, CuO-NWs showed superior antibacterial activity (with minimum inhibitory concentration reached 1.8 µg/mL) over CuO-NPs. The detailed antibacterial activity mechanism of CuO-NWs was further investigated; data proved the precipitation and adsorption of the nanoparticles on the bacterial cell surface leading to cell deformation with reactive oxygen species increment. The results explicated that the nanoparticles shape plays an essential role in the antibacterial activity. Rotational Arc discharge machine might be a promising tool to obtain various metal nanostructures with low cost and environmentally friendly with potent activity.

Design, synthesis and biological evaluation of rhein-piperazine-dithiocarbamate hybrids as potential anticancer agents

A series of novel rhein-piperazine-dithiocarbamate hybrids 3 were efficiently synthesized from rhein through a catalyst-free and one-pot, three-step sequence involving chlorination and N-acylation followed by dithiocarbamate formation. Hybrids 3 were evaluated for their in vitro cytotoxic potency by MTT assay against several human cancer and non-cancer cells. Five of the hybrids were more cytotoxic to human lung cancer cell line A549 than the parent rhein and the reference, cytarabine (CAR). Structure-activity relationship (SAR) analysis indicated that cytotoxicity was significantly enhanced when ester groups were incorporated into the hybrids (3h–j). In particular, hybrid 3h (IC50 = 10.93 μg/mL), containing a long-chain alkyl ester, was the most potent compound toward A549 tumor cells, being 7- and 5-fold more toxic than rhein (IC50 = 77.11 μg/mL) and CAR (IC50 = 49.27 μg/mL), respectively. Additionally, hybrid 3h was less toxic to the corresponding normal human lung fibroblast cell line, WI-38, with a higher selectivity index (SI, WI-38/A549 ≈ 5) than doxorubicin (DOX, SI ≈ 0), CAR (SI ≈ 2) and rhein (SI ≈ 1). Furthermore, hybrid 3h displayed more toxicity against four types of lung cancer cells (A549, Calu-1, PC-9, and H460; IC50 = 10.81–23.78 μg/mL) than against six other types of cancer cells (Huh-7, 786-O, HCT116, Hela, SK-BR-3, and SK-OV-3; IC50 = 23.85–51.98 μg/mL). Further mechanistic studies showed that hybrid 3h induced apoptosis in a concentration-dependent manner in human lung adenocarcinoma cell line PC-9. In vivo safety studies showed that hybrid 3h had no acute toxicity to the major organs of mice and did not lead to blood biochemical index changes. Our results exhibit prominent anti-cancer cell inhibition ability and no obvious systemic toxicity to normal organs, indicating that hybrid 3h has promising potential for further applications in anti-lung cancer drug development.

Phenolic Profiling and In-Vitro Bioactivities of Corn (Zea mays L.) Tassel Extracts by Combining Enzyme-Assisted Extraction.

In this work, enzyme-assisted extraction (EAE) of phenolic compounds from corn tassel using cellulase, protease, and their combination (1:1) was developed and optimized by central composite response surface methodology. The phenolic profile of obtained corn tassel extracts (CTE) was elucidated by high-performance liquid chromatography–diode array detection (HPLC–DAD) analysis, and their antioxidative, antimicrobial, and cytotoxic properties were evaluated in vitro. The results showed that CTE by EAE with combined enzymes had the highest total phenolic content (TPC). Under optimum enzymatic conditions, the experimental TPC values were 9.78, 8.45, and 10.70 mg/g, respectively, which were significantly higher than that of the non-enzymatic control (6.75 mg/g) (p < 0.05). Fourteen more phenolic compounds (13.80–1694.36 µg/g) were identified in CTE by EAE with the combined enzymes, and thus the antioxidant activity of that extract, determined by DPPH and ABTS radical scavenging method, was demonstrated to be stronger than that of the extracts by EAE with the single and ethanol extraction. Furthermore, this extract also showed remarkably better antimicrobial properties against all tested food-borne pathogenic bacteria and mycotoxigenic fungi than CTE by other extraction methods. CTE by EAE were nontoxic to normal lung fibroblast cell line (Wi-38) but cytotoxic to human colorectal and lung cancer cell lines (Caco-2 and A549), with IC50 values of 392.62–461.98 and 210.66–359.56 µg/mL, respectively, which indicated its potential anticancer properties. In conclusion, CTE by EAE, especially with the combined use of cellulase and protease, seems to hold promising potential for multifunctional application in food and pharma fields.

Production of a Polyketide Pigment by Fusarium chlamydosporum

The present study was focused to study the production of secondary metabolite by the fungus, F. chlamydosporum on a non-defined medium with less concentration of nitrogen; the organic nitrogen source being peptone and beef extract. In this context, we have been successful in extracting a polyketide pigment from the fungus by using the homogenization technique. The pigments thus extracted were subjected to various purification techniques via thin layer chromatography, column chromatography, UV-visible spectrophotometry, fourier-transform infrared spectroscopy and finally molecular determination by liquid chromatography coupled to tandem quadrupole mass spectrometry (LC-MS-MS). The polyketide red pigment was finally characterized and identified to be fusarubin following which its cytotoxicity was evaluated in vitro by using normal lung fibroblast cell lines (MRC-5). In the verge of researchers identifying novel compounds for various applications, the production of fusarubin by the fungus can be a major breakthrough as fusarubin has been investigated to exhibit many pharmacological activities. Though fusarubin is reported to be produced by other Fusarium species, this is the foremost study on the production of fusarubin by F. chlamydosporum; the composition of the culture medium is also unique. The production of this polyketide probably correlates in the pathogenesis of F. chlamydosporum as studies comment on this fungus as an opportunistic pathogen.

Zinc(II) Complexes with Dimethyl 2,2′-Bipyridine-4,5-dicarboxylate: Structure, Antimicrobial Activity and DNA/BSA Binding Study

Two zinc(II) complexes with dimethyl 2,2′-bipyridine-4,5-dicarboxylate (py-2py) of the general formula [Zn(py-2py)X2], X = Cl− (1) and Br− (2) were synthesized and characterized by NMR, IR and UV-Vis spectroscopy and single-crystal X-ray diffraction analysis. Complexes 1 and 2 are isostructural and adopt a slightly distorted tetrahedral geometry with values of tetrahedral indices τ4 and τ’4 in the range of 0.80–0.85. The complexes were evaluated for their in vitro antimicrobial activity against two bacterial (Pseudomonas aeruginosa and Staphylococcus aureus) and two fungal strains (Candida albicans and Candida parapsilosis), while their cytotoxicity was tested on the normal human lung fibroblast cell line (MRC-5) and the model organism Caenorhabditis elegans. Complex 1 showed moderate activity against both Candida strains. However, this complex was twofold more cytotoxic compared to complex 2. The complexes tested had no effect on the survival rate of C. elegans. Complex 2 showed the ability to inhibit filamentation of C. albicans, while complex 1 was more effective than complex 2 in inhibiting biofilm formation. The interactions of complexes 1 and 2 with calf thymus DNA (ct-DNA) and bovine serum albumin (BSA) were studied to evaluate their binding affinity toward these biomolecules.

Design, synthesis and anticancer activity studies of novel 4-butylaminophenyl hydrazide-hydrazones as apoptotic inducers

In this study, a series of the novel Tetracaine derivatives bearing hydrazide-hydrazone moiety were designed, synthesized, and evaluated for anticancer activity. The structures of these compounds were characterized by spectral (1H–13C NMR, FT-IR, and HR-MS analyses) methods. All synthesized compounds (2a-l) were screened for anticancer activity against human hepatocellular carcinoma (HepG2) and lung carcinoma (A549) cell lines. Against HepG2 and A549 cell lines, among the synthesized compounds, 4-(Butylamino)-N'-[(2,4-dichlorophenyl)methylidene]benzohydrazide (2i) demonstrated the most potent anticancer activity with IC50 values 28 and 7 μM, respectively. Possible cytotoxic effects of compounds (2a-l) on both normal human lung fibroblast (MCR-5) and normal human dermal fibroblast (HDF) cell lines were assessed. Inhibition of anti-apoptotic protein Bax and Bcl-2 was investigated in HepG2 and A549 cells treated with compound 2i using qRT-PCR. Apoptosis was also detected by Annexin V studies. The flow cytometric analysis results showed that compound 2i treatment of HepG2 and A-549 cells significantly increased apoptotic cell populations while decreasing viabilities in these carcinomas in a dose-dependent manner after 72 h of incubation.

Proteomic Analysis Reveals Differential Expression Profiles in Idiopathic Pulmonary Fibrosis Cell Lines.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, irreversible lung disorder of unknown cause. This disease is characterized by profibrotic activation of resident pulmonary fibroblasts resulting in aberrant deposition of extracellular matrix (ECM) proteins. However, although much is known about the pathophysiology of IPF, the cellular and molecular processes that occur and allow aberrant fibroblast activation remain an unmet need. To explore the differentially expressed proteins (DEPs) associated with aberrant activation of these fibroblasts, we used the IPF lung fibroblast cell lines LL97A (IPF-1) and LL29 (IPF-2), compared to the normal lung fibroblast cell line CCD19Lu (NL-1). Protein samples were quantified and identified using a label-free quantitative proteomic analysis approach by liquid chromatography-tandem mass spectrometry (LC-MS/MS). DEPs were identified after pairwise comparison, including all experimental groups. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein–Protein Interaction (PPI) network construction were used to interpret the proteomic data. Eighty proteins expressed exclusively in the IPF-1 and IPF-2 clusters were identified. In addition, 19 proteins were identified up-regulated in IPF-1 and 10 in IPF-2; 10 proteins were down-regulated in IPF-1 and 2 in IPF-2 when compared to the NL-1 proteome. Using the search tool for retrieval of interacting genes/proteins (STRING) software, a PPI network was constructed between the DEPs and the 80 proteins expressed exclusively in the IPF-2 and IPF-1 clusters, containing 115 nodes and 136 edges. The 10 hub proteins present in the IPP network were identified using the CytoHubba plugin of the Cytoscape software. GO and KEGG pathway analyses showed that the hub proteins were mainly related to cell adhesion, integrin binding, and hematopoietic cell lineage. Our results provide relevant information on DEPs present in IPF lung fibroblast cell lines when compared to the normal lung fibroblast cell line that could play a key role during IPF pathogenesis.

Structural characterization and antimicrobial evaluation of chromium(III) and cobalt(III) complexes with 2,2-diMe-1,3-pdta: Tuning dimensionality of coordination polymer and the water content by alkyl substitution

Hexadentate 2,2-dimethyl-1,3-propanediamine-N,N,N’,N’-tetraacetate (2,2-diMe-1,3-pdta) ligand, containing two methyl substituents at the central carbon atom of a 1,3-propanediamine, has been prepared and used for the synthesis of Na[Cr(2,2-diMe-1,3-pdta)]·3.75H2O (1) and Na[Co(2,2-diMe-1,3-pdta)]·3.88H2O (2) complexes. These complexes were characterized by IR and electronic absorption spectroscopy, and single-crystal X-ray diffraction analysis. NMR (1H and 13C) spectroscopy was additionally applied for the characterization of complex 2. Crystallographic data indicate that the two investigated crystals are isostructural and contain 2,2-diMe-1,3-pdta ligand coordinated to metal ion through 2N and 4O atoms forming an octahedral complex in which the six-membered 1,3-propanediamine chelate ring adopts a twist-boat conformation. There are four such complex anions in the symmetry independent part of the unit cell. Each complex anion is further connected to the sodium counterion(s) via the bridging carboxylate group(s). Structural changes in 2,2-diMe-1,3-pdta-Cr(III) complex stimulated solely by the presence of alkyl side groups are discussed. The present study shows that in 1,3-pdta-type complexes of Cr(III) and Co(III), the environment at coordination centre can be modified by introducing substitution in one of the carbon atoms of the diamine and the resulting difference in the subunit structure can bring about noticeable change in molecular and crystal structure. The examples illustrate the importance of the steric effect for the fine tuning of the dimensionality of the resulting coordination polymer and the water content. The antimicrobial activity of complexes 1 and 2 was evaluated against different bacterial and Candida spp., while their cytotoxic effects were tested on the normal human lung fibroblast cell line (MRC-5).