WI-38 Cells Research Articles

Assessment of antimicrobial, cytotoxicity, and antiviral impact of a green zinc oxide/activated carbon nanocomposite

This work deals with the synthesis of zinc oxide nanoparticles/activated carbon (ZnO NPs/AC) nanocomposites with different weight ratios (3:1, 1:1, and 1:3), where the antimicrobial, antiviral, and cytotoxicity impact of the formulated nanocomposites were evaluated versus the crude ZnO and AC samples. The formula (3:1; designated Z3C1) exhibited the utmost bactericidal effect against Gram positive group, unicellular and filamentous fungi. Regarding Gram negative group, the sample (Z3C1) was remarkably effective against Klebsiella pneumonia, unlike the case of Escherichia coli. Moreover, the whole samples showed negligible cytotoxicity against the human WI38 cell line, where the most brutality (4%) was exerted by 1000 µg/mL of the formula (Z1C3). Whilst, the formula (Z3C1) exerted the apical inhibition impact against Herpes simplex (HSV1) virus. Consequently, the synthesized (Z3C1) nanocomposite was sorted out to be fully characterized via different physicochemical techniques including FTIR, XRD, SEM, TEM, Zeta potential, TGA, and BET. XRD indicated a predominance of the crystalline pattern of ZnO NPs over the amorphous AC, while the FTIR chart confirmed an immense combination between the ZnO NPs and AC. SEM, TEM, and size distribution images illustrated that the fabricated ZnO NPs/AC was in the nanoscale size swung from 30 to 70 nm. The distinctive surface area of composite material, recording 66.27 m2/g, clearly disclosed its bioactivity toward different bacterial, fungal, and virus species.

LncRNA LINC00707 serves as a sponge of miR-382-5p to alleviate lipopolysaccharide (LPS)-induced WI-38 cell injury through upregulating NKAP in infantile pneumonia

Infantile pneumonia (IP) is an acute lower respiratory infection that imposes a heavy burden on children’s health. Increasing evidence has demonstrated that long non-coding RNA (lncRNA) LINC00707 participates in the regulation of the pneumonia process. Cell proliferative ability and apoptosis were measured using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2’-deoxyuridine (EdU), and flow cytometry assays. Bcl-2 related X protein (Bax), NF-kB activating protein (NKAP), p-P65, P65, p-IκBα, and IκBα protein levels were detected using western blot assay. The binding between miR-382-5p and LINC00707 or NKAP was predicted by starBase v2.0 and then verified by a dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. LINC00707 and NKAP levels were increased, and miR-382-5p was decreased in LPS-stimulated WI-38 cells. Furthermore, the silencing of LINC00707 could abrogate LPS-engendered WI-38 cell proliferation, apoptosis, and oxidative stress. LINC00707 deficiency could relieve LPS-triggered WI-38 cell damage by regulating the miR-382-5p/NKAP axis, providing a new therapeutic strategy for IP treatment.

Helicobacter pylori promotes inflammatory factor secretion and lung injury through VacA exotoxin-mediated activation of NF-κB signaling

ABSTRACT Previous reports have shown that Helicobacter pylori (H. pylori) infection is associated with respiratory diseases. However, the pathogenesis remains unclear. Vacuolating cytotoxin A (VacA) is a major H. pylori exotoxin. In this study, we investigated the signaling pathways involved in the inflammatory response to H. pylori infection and VacA. Mice were treated with H. pylori and VacA, and histopathological analysis of lung tissues was performed using hematoxylin-eosin, Masson’s trichrome, and periodic acid Schiff staining. The secretion of inflammatory cytokines was evaluated by enzyme-linked immunosorbent assay. The expression of VacA, nuclear factor-kappa B (NF-κB), and p65 NF-κB was analyzed by Western blotting and immunofluorescence. Cell proliferation and apoptosis were assessed using the MTS assay and flow cytometry, respectively. In mice, H. pylori infection and VacA treatment promoted the secretion of the inflammatory factors interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), IL-6, and IL-8, increased p65 NF-κB protein phosphorylation, and induced lung injury. Furthermore, H. pylori infection promoted VacA production. In an in vitro cell model, VacA treatment significantly suppressed the proliferation of WI-38 and BEAS-2B cells, promoted apoptosis, induced TNF-α, IL-1β, IL-6, and IL-8 secretion, and promoted p65 NF-κB protein phosphorylation and NF-κB nuclear transfer. The NF-κB inhibitor BAY11-7082 alleviated VacA-induced inflammation and apoptosis and increased cell viability. In conclusion, VacA promotes the secretion of inflammatory factors and induces lung injury through NF-κB signaling.

Knockdown of EPSTI1 alleviates lipopolysaccharide-induced inflammatory injury through regulation of NF-κB signaling in a cellular pneumonia model.

Although early diagnosis, antibiotic therapies, corticosteroid application, and health care services are conventional managements for pneumonia, antibiotic resistance and adverse reactions remain as limitations for pneumonia treatment. The study attempted to evaluate the potential role of EPSTI1 against pneumonia and reveal its underlying mechanism. Lipopolysaccharide (LPS) (5, 10, and 20 μg/mL) was applied in WI-38 cells to establish the in vitro pneumonia model. Knockdown of epithelial-stromal interaction 1 (EPSTI1) was performed by transfection with EPSTI1 siRNA (siEPSTI1) into LPS-treated cells. Cell Counting Kit-8 assays were implemented to measure cell viability, and apoptotic cells were detected using flow cytometry. Interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) were quantified using enzyme-linked immunosorbent assay (ELISA). Immunoblotting and quantitative real-time polymerase chain reaction (qRT-PCR) were conducted to quantify EPSTI1 expression, and proteins related to nuclear factor κ-light-chain-enhancer of activated B cell (NF-κB) signaling, including p-p65, p65, p-IκBα, and IκBα. EPSTI1 was highly expressed in LPS-treated WI-38 cells. Cell apoptosis was promoted, and cell viability was inhibited after being exposed to LPS. Besides, IL-1β, IL-6, and TNF-α were dramatically upregulated. Knockdown of EPSTI1 restored cell viability, inhibited cell apoptosis, and attenuated expressions of proinflammatory factors. Additionally, knockdown of EPSTI1 visibly decreased the increased ratios of p-p65/p65 and p-IκBα/IκBα induced by LPS. Knockdown of EPSTI1 alleviated inflammatory injury through the inactivation of the NF-κB pathway. These results provided promising management in preventing pneumonia in patients.

CircTRHDE knockdown protects WI-38 cells against LPS-induced inflammatory injury

Background Circular RNAs (circRNAs) have been reported to be involved in the progression of infantile pneumonia. Here, we investigated the function of circTRHDE in lipopolysaccharide (LPS)-induced cell inflammatory injury to evaluate its role in infantile pneumonia progression. Methods The circTRHDE, microRNA (miR)-381-3p and TNF-receptor associated factor 3 (TRAF3) expression were detected by quantitative real-time PCR. LPS-induced WI-38 cells were used to construct an inflammatory injury model. Cell viability, inflammation and apoptosis were measured by cell counting kit assay, ELISA assay and flow cytometry. Caspase3 activity, MDA level and SOD activity were analysed to assess cell apoptosis and oxidative stress. Protein levels were determined using western blot analysis. The interaction between miR-381-3p and circTRHDE or TRAF3 was confirmed by dual-luciferase activity assay and RNA pull-down assay. Results CircTRHDE had increased expression in infantile pneumonia patients and LPS-induced WI-38 cells. LPS treatment inhibited WI-38 cell viability while promoting inflammation, apoptosis and oxidative stress. However, knockdown of circTRHDE remitted LPS-triggered WI-38 cell injury. CircTRHDE could sponge miR-381-3p to positively regulate TRAF3 expression. MiR-381-3p suppressed LPS-induced WI-38 cell inflammatory injury, and this effect was revoked by TRAF3 overexpression. Also, LPS-induced WI-38 cell inflammatory injury restrained by circTRHDE knockdown also were reversed by miR-318-3p inhibitor or TRAF3 overexpression. Conclusion Our findings demonstrated that circTRHDE might be a target for infantile pneumonia treatment, which relieved LPS-induced cell inflammatory injury by the regulation of the miR-318-3p/TRAF3 axis.

Antifungal Activities of Sulfur and Copper Nanoparticles against Cucumber Postharvest Diseases Caused by Botrytis cinerea and Sclerotinia sclerotiorum.

Nanoparticles (NPs) have attracted great interest in various fields owing to their antimicrobial activity; however, the use of NPs as fungicides on plants has not been sufficiently investigated. In this study, the antifungal activities of sulfur nanoparticles (S-NPs) and copper nanoparticles (Cu-NPs) prepared by a green method were evaluated against Botrytis cinerea and Sclerotinia sclerotiorum. The formation of NPs was confirmed by transmission electron microscopy (TEM) and X-ray diffraction analysis (XRD). The antifungal activities of NPs (5–100 µg/mL), CuSO4 (4000 µg/mL), and micro sulfur (MS) were compared to those of the recommended chemical fungicide Topsin-M 70 WP at a dose of 1000 µg/mL. They were evaluated in vitro and then in vivo at different temperatures (10 and 20 °C) on cucumber (Cucumis sativus) fruits. The total phenolic content (TPC) and total soluble solids (TSS) were determined to study the effects of various treatments on the shelf life of cucumber fruits, compared to untreated cucumber as a positive control. The diameters of S-NPs and Cu-NPs ranged from 10 to 50 nm, and 2 to 12 nm, respectively. The results revealed that S-NPs exhibited the highest antifungal activity, followed by Cu-NPs. However, CuSO4 showed the lowest antifungal activity among all treatments. The antifungal activity of the prepared NPs increased with the increase in NP concentration, while the fungal growth was less at low temperature. The cytotoxicity of the prepared NPs was evaluated against the WI-38 and Vero cell lines in order to assess their applicability and sustainability. S-NPs caused less cytotoxicity than Cu-NPs.

Development of fluorinated nicotinonitriles and fused candidates as antimicrobial, antibiofilm, and enzyme inhibitors.

The antimicrobial assessments of two new series of nicotinonitriles and pyrido[2,3-d]pyrimidines were performed using amoxicillin and nystatin as reference standards. Outstanding antifungal activities were achieved by some target compounds; for instance, compounds 7 and 9 displayed a minimal inhibitory concentration (MIC) value of 1.95 µg/ml toward Candida albicans, compound 11 showed a potent anti-Rhizopus effect (MIC 1.95 µg/ml) and compound 14 elicited remarkable antifungal effects against both Aspergillis niger and C. albicans (MIC 1.95 µg/ml). However, pyrido[2,3-d]pyrimidines 12, 14, and 16 showed moderate antibacterial activities against some gram-negative bacteria. The antibiofilm results of these compounds against resistant strains of Proteus mirabilis were better than those of Pseudomonas aeruginosa. Docking studies of these hits at the DNA gyrase active site revealed affinity and docking scores comparable to that of the reference standards. Gyrase-inhibitory activities revealed that 14 (IC50 = 0.31 µM) is the most potent hit as DNA gyrase A inhibitor; it exhibited 1.66-fold the activity of ciprofloxacin (IC50 = 0.50 µM) and it was a 44.3 times more potent gyrase B inhibitor (IC50 = 0.04 µM) than novobiocin (IC50 = 1.77 µM). Regarding its antifungal activity, it displayed 0.78% of the fluconazole activity as a 14α-demethylase inhibitor. The cytotoxicity of 12, 14, and 16 on human diploid lung fibroblasts (WI38 cells) ensured their safety. Moreover, they are orally bioavailable with no permeation of the blood-brain barrier.

Anti-Cancer Activity of Buthus occitanus Venom on Hepatocellular Carcinoma in 3D Cell Culture.

Hepatocellular carcinoma (HCC) is the most dominant primary liver cancer, which can be caused by chronic hepatitis virus infections and other environmental factors. Resection, liver transplantation, and local ablation are only a few of the highly effective and curative procedures presently accessible. However, other complementary treatments can reduce cancer treatment side effects. In this present work, we evaluated the activity of Moroccan scorpion venom Buthus occitanus and its fractions obtained by chromatography gel filtration against HCC cells using a 3D cell culture model. The venom was fractionated by gel filtration chromatography, each fraction and the crude venom was tested on normal hepatocytes (Fa2N-4 cells). Additionally, the fractions and the crude venom were tested on MCTSs (multicellular tumor spheroids), and this latter was generated by cultivate Huh7.5 cancer cell line with WI38 cells, LX2 cells, and human endothelial cells (HUVEC). Our results indicate that Buthus occitanus venom toxin has no cytotoxic effects on normal hepatocytes. Moreover, it is reported that F3 fraction could significantly inhibit the MCTS cells. Other Protein Separation Techniques (High-performance liquid chromatography) are needed in order to identify the most active molecule.

The Traditional Chinese Medicine Formula Jing Guan Fang for Preventing SARS-CoV-2 Infection: From Clinical Observation to Basic Research.

COVID-19 is a global epidemic. Developing adjuvant therapies which could prevent the virus from binding to cells may impair viral infection. This study produces a traditional Chinese medicine formula, Jing Guan Fang (JGF), based on ancient medical texts, and examines the efficacy and the mechanism by which JGF prevents viral infections. JGF reduces COVID-19 like symptoms. Functional studies show that JGF inhibits the formation of syncytium and reduces the formation of viral plaque. JGF is not toxic in vitro and in vivo. Mechanistically, JGF induces lysosomal-dependent ACE2 degradation and suppresses mRNA and the protein levels of TMPRSS2 in human lung WI-38 and MRC-5 cells. Mice that inhale JGF exhibit reduced ACE2 and TMPRSS2 protein levels in lung tissues. Together, these findings suggest that JGF may improve the COVID-19 like symptoms and inhibit viral infection. Moreover, JGF may be applicable as an adjuvant preventive strategy against SARS-CoV-2 infection in addition to the use of vaccines.

New AKT-dependent mechanisms of anti-COVID-19 action of high-CBD Cannabis sativa extracts

COVID-19 is caused by the SARS-CoV-2 virus, which enters target cells via interactions with ACE2 and TMPRSS2. Here, we show AKT serine/threonine kinase-dependent epigenetic control of ACE2 and TMPRSS2 expression by high-cannabidiol (CBD) cannabis extracts and their individual components. CBD alone and extracts #1, #5, #7, and #129 downregulated ACE2 and TMPRSS2 in lung fibroblast WI-38 cells through AKT-mediated inhibition. miR-200c-3p and let-7a-5p were two contributing miRNAs in CBD-mediated suppression of ACE2 and TMPRSS2. CBD and terpene PTWT2.2 profoundly inhibited ACE2 and TMPRSS2 expression, both individually and in combination. Extracts #1, #5, #7, and #169 suppressed COX2 expression and remarkably attenuated TNFα/IFNγ-triggered induction of proinflammatory factors IL-6 and IL-8 by AKT pathway. The most abundant molecules present in extracts #1 and #7 modulated the expression of COX2, IL-6, and IL-8 both individually and in combination. These results reveal that high-CBD cannabis extracts attenuated ACE2 and TMPRSS2 expression and the induction of inflammatory mediators COX2, IL-6, and IL-8 via the AKT pathway, highlighting their potential anti-COVID-19 features.

Copper(II) Complexes of Halogenated Quinoline Schiff Base Derivatives Enabled Cancer Therapy through Glutathione-Assisted Chemodynamic Therapy and Inhibition of Autophagy Flux.

Twelve new complexes Cu(L1)2-Cu(L12)2 were designed and synthesized to improve their chemotherapeutic properties. They showed considerable antiproliferative activity against T24 cancer cells but lower cytotoxicity to human normal cells HL-7702 and WI-38. A mechanism study indicated that Cu(L4)2 and Cu(L10)2 were reduced to Fenton-like Cu+ by glutathione depletion, and the resulting Cu+ catalyzed the generation of highly toxic hydroxyl radicals from excess H2O2. Simultaneously, Cu(L4)2 and Cu(L10)2 could decrease the catalase activity to restrain H2O2 transfer to H2O for enhanced chemodynamic therapy (CDT). These induced mitochondrial dysfunctions and endoplasmic reticulum stress to induce T24 cell apoptosis. In addition, Cu(L4)2 and Cu(L10)2 inhibited autophagy flux to promote cell apoptosis. Cu(L4)2 and Cu(L10)2 demonstrated strong tumor inhibition ability in the T24 xenograft model. Moreover, Cu(L10)2 showed higher antitumor activity and a better safety profile than the CDT agent Cu1. Cu(L10)2 exhibited excellent pharmacokinetic properties. Collectively, Cu(L4)2 and Cu(L10)2 could be developed as potential CDT candidates for cancer treatment.

TRIM27 suppresses inflammation injuries in pediatric pneumonia by targeting TLR4/NF-κB signaling pathway.

Pneumonia widely occurs in children and has high global morbidity and mortality. There is an urgent requirement to clarify the underlying mechanism of pediatric pneumonia and definite its potential therapeutic targets. Tri-domain protein 27 (TRIM27) is one of the TRIM protein family members which widely participated in multiple cellular processes. To assess whether TRIM27 protects against pediatric pneumonia. A lipopolysaccharide (LPS)-induced inflammation injury model was constructed. The level of TRIM27 in LPS-induced cells was examined. The effects of TRIM27 in cell apoptosis and inflammatory response was evaluated. Moreover, the involvement of TLR4/NF-κB pathway were detected by Immunoblot. We established a lipopolysaccharide (LPS)-induced inflammation injury model. Our data confirmed that LPS-treated WI-38 cells demonstrated a down-regulated expression of TRIM27. Overexpression of TRIM27 effectively reduced apoptosis and up-regulated the inflammatory factors in LPS-treated WI-38 cells. Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) pathway acted as a key point in LPS-mediated inflammation injuries, and overexpression of TRIM27 remarkably inhibited the activity of TLR4/NF-κB pathway, indicating the anti-inflammatory effect of TRIM27. In conclusion, TRIM27 protects WI-38 cells against LPS-induced inflammation injuries by inhibiting TLR4/NF-κB pathway.

Improvement of the pharmacokinetics and antifibrotic effects of nintedanib by intrapulmonary administration of a nintedanib–hydroxypropyl-γ-cyclodextrin inclusion complex in mice with bleomycin-induced pulmonary fibrosis

Idiopathic pulmonary fibrosis is a chronic lung disease that is characterized by progressive abnormal reprogramming following injury of the pulmonary structure. In this study, we prepared a nintedanib (antifibrotic agent) and cyclodextrin (CyD) inclusion complex to improve the pharmacokinetics and antifibrotic effects of nintedanib following intrapulmonary administration. Hydroxypropyl-γ-CyD (HP-γ-CyD) enhanced the solubility of nintedanib without cytotoxic effects on WI-38 cells (lung fibroblasts) and NCI-H441 cells (alveolar epithelium model). Compared with nintedanib ethanesulfonate salt, the nintedanib–HP-γ-CyD inclusion complex exhibited prolonged distribution in the lungs following intrapulmonary administration in mice with bleomycin-induced pulmonary fibrosis. In addition, compared with nintedanib ethanesulfonate salt, the nintedanib–HP-γ-CyD inclusion complex exhibited higher stability in the bronchoalveolar lavage fluid and lower permeability in NCI-H441 cell monolayers. These results suggested that the inclusion complexation of nintedanib into HP-γ-CyD improved its pharmacokinetics following intrapulmonary administration by increasing its stability in the lungs and reducing its permeability through the alveolar cell membrane. Intrapulmonary administration of the nintedanib–HP-γ-CyD inclusion complex significantly reduced the intrapulmonary hydroxyproline content and limited pathological fibrotic changes. Overall, this study indicates that antifibrotic agent–CyD inclusion complexation intended for intrapulmonary administration can be used to prolong distribution in the lungs and lead to the expansion of idiopathic pulmonary fibrosis therapy.

Skullcapflavone II Alleviates Lipopolysaccharide-Induced Apoptosis and Inflammation in WI-38 Cells

The role of skullcapflavone II in pneumonia was investigated using lipopolysaccharide treated human lung fibroblasts WI-38 cells as a model. Lipopolysaccharide treatment led to decreased cell viability, increased cell apoptosis and inflammation. Exposure of these lipopolysaccharide-treated cells to skullcapflavone II resulted in amelioration of cytotoxic effects of the lipopolysaccharide. The reduced IκBα expression and enhanced p-IκBα and p-p65 in WI-38 cells caused by the lipopolysaccharide treatment were reversed by skullcapflavone II. In conclusion, skullcapflavone II exerts antiapoptotic and anti-inflammatory effects on lipopolysaccharide-induced WI-38 through inhibition of NF-κB pathway.

Fabrication, characterization and in vitro evaluation of disulfiram-loaded cellulose acetate/poly(ethylene oxide) nanofiber scaffold for breast and colon cancer cell lines treatment

Cancer and microbial infections threaten human health. Currently, chemotherapeutic drugs for cancer lack selectivity between normal and cancer cells, exacerbating this problem. Effective anticancer drug encapsulation is the golden key to solving this issue. Disulfiram (DS), an anticancer drug, has low solubility and selectivity and to tackle this concern, cellulose acetate (CA) and poly (ethylene oxide) (PEO) was selected as a matrix to prepare nanofiber containing DS (DS@CA/PEO) via electrospinning technique. DS@CA/PEO nanofiber was characterized by SEM, FTIR, TGA, and X-rd patterns and the results confirmed DS incorporation in CA/PEO nanofiber. DS@CA/PEO nanofiber scaffold showed higher safety than DS-free on human normal cells (Wi-38) with revealing similar anticancer activity of DS-free against colon cancer line (Caco-2) and breast cancer line (MDA-MB 231). This higher selectivity of DS@CA/PEO towards cancer cells than normal cells was associated with maintaining apoptotic activity and aldehyde dehydrogenase-inhibitory potency of DS. The latter efficacy led to eradicating colon and breast cancer stem cells, as evidenced by flow cytometry. Moreover, DS@CA/PEO nanofiber scaffold showed potent antibacterial activity (in vitro) against both Gram-negative and Gram-positive bacteria. These results investigated that DS@CA/PEO nanofiber scaffold could be a potential dual candidate as a selective anticancer and antimicrobial agent.

Novel insights from a multiomics dissection of the Hayflick limit.

The process wherein dividing cells exhaust proliferative capacity and enter into replicative senescence has become a prominent model for cellular aging in vitro. Despite decades of study, this cellular state is not fully understood in culture and even much less so during aging. Here, we revisit Leonard Hayflick's original observation of replicative senescence in WI-38 human lung fibroblasts equipped with a battery of modern techniques including RNA-seq, single-cell RNA-seq, proteomics, metabolomics, and ATAC-seq. We find evidence that the transition to a senescent state manifests early, increases gradually, and corresponds to a concomitant global increase in DNA accessibility in nucleolar and lamin associated domains. Furthermore, we demonstrate that senescent WI-38 cells acquire a striking resemblance to myofibroblasts in a process similar to the epithelial to mesenchymal transition (EMT) that is regulated by t YAP1/TEAD1 and TGF-β2. Lastly, we show that verteporfin inhibition of YAP1/TEAD1 activity in aged WI-38 cells robustly attenuates this gene expression program.

Synthesis, in-silico, and in-vitro study of novel chloro methylquinazolinones as PI3K-δ inhibitors, cytotoxic agents

The PI3k-δ enzyme is of the key enzymes for cellular growth and proliferation. One of the key mechanisms for cytotoxic agents is to target the PI3k-δ enzyme. 5c and 5d were able to bind at ATP binding pocket of PI3k-δ enzyme in an inhibitory mode forming H -bond interaction with key amino acid Val828. 5c and 5d showed in-v itro inhibition of PI3k-δ enzyme(IC 50 =8.27±0.19μM), (IC 50 =1.24±0.03μM) respectively. 5c and 5d showed moderated to good in-vitro cytotoxicity against three cell lines HCT (IC 50 =8.00 ±0.12 μM), (IC 50 =47.56 ±0.67 μM), MCF-7 (IC 50 =21.22 ±0.33 μM), (IC 50 =41.07 ±0.58 μM) and HePG-2(IC 50 =58.98 ±0.33 μM), (IC 50 =17.78 ±0.58 μM), respectively. 5c and 5d showed in-vitro cytotoxicity against the WI-38 cell line (IC 50 =177.00±3.66μM), (IC 50 =148.49±1.37μM), respectively. Through a two-step procedure, 3-amino-7-chloro-2-methylquinazolin-4(3 H )-one was synthesized from 2-amino-4-chlorobenzoic acid as a starting material. The latter reacted with chloro acetylchloride, then nucleophilically substituted with various secondary amines to produce acetamide derivatives ( 5a-e ), or underwent condensation reaction with various aldehydes to produce arylidine derivatives ( 6a-e ). In-silico study of drug-likeness and ADME descriptors was conducted for all compounds. Compounds showed good oral bioavailability, as well as good gastrointestinal absorption potential and no symptoms of liver or CNS adverse effects. In-vitro cytotoxic activity of the compounds was moderate to good when compared to staurosporine in three cell lines: HCT, MCF-7, and HepG-2. Compound 5c showed the highest cytotoxic activity against the HCT cell line (IC 50 = 8.00 ± 0.33 μM), Compound 5d showed the highest cytotoxic activity against the HepG-2 cell line (IC 50 = 17.78 ± 0.58 μM). Acetamide derivatives revealed higher cytotoxic activity compared to arylidine derivatives. Compound 5d had the highest enzyme inhibition activity in the in-vitro PI3k-δ enzyme inhibition assay (IC 50 = 1.24 ± 0.03 μM) followed by 5c (IC 50 = 8.27 ± 0.19 μM). Both 5c and 5d were able to bind at the ATP binding site of the PI3k-δ enzyme in a mode similar to the native ligand where they formed H -bond interactions with the hinge region amino acid Val828 and hydrophobic interactions with other amino acids indicating an agreement between molecular docking simulation study and the biological screening.

Pyrazoles and Fused Pyrimidines: Synthesis, Structure Elucidation, Antitubercular Activity and Molecular Docking Study.

Synthesis of new heterocyclic drugs in short reaction time with sufficient quantity is considered as a target for several pharmaceutical scientists. Thus, organic reactions proceeded on the surface of nano-sized catalysts to speed up the stimulation process. <p Objective: We aimed in this research to synthesize a new series of heterocyclic compounds carrying pyrazole moiety in the presence of ZnO nano-catalyst to investigate their anti-tubercular activity. ZnO(NPs) were used in the synthesis of novel series of thienylpyrazolopyrimidines bearing arylazo group by the reaction of thiophene-enaminone and the amino-arylazopyrazoles in excellent yield. On the other hand, another series of theinyl-pyrazoles was synthesized through the reaction of the same enaminone with hydrazonoyl chlorides, but the usage of ZnO(NPs) failed in such reactions. The proposed structures of the products and the mechanistic pathways of the reactions were assured based on the spectral data and chemical evidences. Thienylpyrazole derivatives were assessed for their activity as Mycobacterium tuberculosis inhibitor and their results revealed that two thienylpyrazole derivatives 24d & 24f showed the most significant anti-mycobacterial activity with MIC values 0.70 & 1.29 μM/mL, respectively comparing with the MIC value = 0.60 μM/mL of the standard drug Rifampicin. Furthermore, the most active thienylpyrazole derivatives were investigated for their cytotoxic impact versus normal cells WI-38 (Normal human Lung fibroblast cells) using MTT assay. These thienylpyrazole derivatives exhibited good selective index profile. Moreover, 1,3,4-trisubstituted pyrazole analogs showed good interaction with the active site of enoyl-acyl carrier protein reductase (Mt InhA) through molecular docking studies. We synthesized a new series of heterocyclic compounds carrying pyrazole moiety in the presence of ZnO nano-catalyst as anti-tubercular agents.

Bioactive properties of nanofibers based on poly(vinylidene fluoride) loaded with oregano essential oil: Fabrication, characterization and biological evaluation

Essential oils have promising therapeutic potentials (antioxidant, anti-inflammatory, and antibacterial activities). However, its instability (volatility and easily degradation) represents a big challenge for using them as a therapeutic agent. This study describes encapsulation of oregano essential oil (OEO) into poly(vinylidene fluoride) polymer (PVDF) through electrospinning to extend and preserve their bioactive properties (OEO@PVDF). Bead free and homogenous nanofibers formation was confirmed by scanning electron microscopy (SEM). Successful OEO incorporation was confirmed by Fourier transform infrared spectroscopy (ATR-FTIR). Hydrophobicity of OEO@PVDF nanofiber scaffold was unaffected by OEO integration. Biocompatibility of OEO@PVDF nanofiber scaffold on human normal cells (Wi-38) showed safety and apoptosis-mediated anticancer activity of OEO was enhanced. OEO@PVDF nanofiber scaffold had strong antioxidant and anti-cancer activities even after 6 months of storage at room temperature compared to OEO-free. Our study reports a simple and effective method to prepare OEO@PVDF nanofiber scaffold and opens up many new applications of essential oils for different applications.

Synthesis and biological evaluation of prodrugs for nitroreductase based 4-β-amino-4′-Demethylepipodophyllotoxin as potential anticancer agents

A series of prodrugs for nitroreductase (NTR) based 4-β-amino-4′- Demethylepipodophyllotoxin as potential anticancer agents were synthesized, and their antiproliferative activities in vitro showed compounds 2b (IC50 = 0.77, 0.83 and 1.19 μM) and 2d (IC50 = 0.98, 0.91 and 1.58 μM) were greatly selectively toxic to tumor cells A-549, HeLa and HepG2, respectively, and lower damage to normal WI-38 cells in comparison with positive agent Etoposide and Demethylepipodophyllotoxin, and induced cell cycle arrest in the G2/M phase with a concomitant decrease in the population of G1 phase in HeLa cells, which were accompanied by apoptosis. Furthermore, Molecular docking model showed that compounds 2b and 2d appeared to form stable bonds with NTR 1DS7. Taken together, these conjugates have the potential to be developed as antitumor drugs.